Polymer compositions containing grafted polymeric networks and processes for their preparation and use

ABSTRACT

Provided are polymer compositions made by a process comprising: (a) providing a first reactive composition containing: (i) a polymerization initiator that is capable, upon a first activation, of forming two or more free radical groups, at least one of which is further activatable by subsequent activation; (ii) one or more ethylenically unsaturated compounds; and (iii) a crosslinker; (b) subjecting the first reactive composition to a first activation step such that the first reactive composition polymerizes therein to form a crosslinked substrate network containing a covalently bound activatable free radical initiator, (c) combining the crosslinked substrate network with a second reactive composition containing one or more ethylenically unsaturated compounds; and (d) activating the covalently bound activatable free radical initiator of the crosslinked substrate network such that the second reactive composition polymerizes therein with the crosslinked substrate network to form a grafted polymeric network and a byproduct polymer. Also provided are precursors to the polymer compositions, processes for preparation of the polymer compositions, and methods of using the polymer compositions, for instance in medical devices.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/371,362, filed Aug. 5, 2016, which is incorporated herein byreference in its entirety.

FIELD OF THE INVENTION

The invention relates to polymer compositions that contain graftedpolymeric networks and processes for preparing the polymer compositions.The invention also relates to precursors of the polymer compositions,processes for preparing the precursors, as well as methods of using thepolymer compositions, for instance in medical devices.

BACKGROUND OF THE INVENTION

The development of polymer materials prepared from individual componentsthat contribute desirable properties is an ongoing goal in many productareas. For instance, polymer materials displaying oxygen permeabilityand hydrophilicity are desirable for a number of applications within themedical devices area, such as in contact lenses.

A commonly encountered challenge when forming polymeric materials thatattempt to combine properties is that, in many cases, the individualcomponents from which the final material is made are not readilycompatible with each other. For instance, in the contact lens field,silicone hydrogels have been found to provide lenses with significantlyincreased oxygen permeability and therefore are capable of reducingcorneal edema and hyper-vasculature, conditions that may sometimes beassociated with conventional hydrogel lenses. Silicone hydrogels havetypically been prepared by polymerizing mixtures containing at least onesilicone-containing monomer or reactive macromer and at least onehydrophilic monomer. However, silicone hydrogel lenses can be difficultto produce because the silicone components and the hydrophiliccomponents are often incompatible.

New technologies for creating polymer materials, including where thecomponents are otherwise incompatible, are desirable in many fields,including medical devices.

SUMMARY OF THE INVENTION

We have now found that processes as described herein are capable ofproviding new compositions derived from a wide variety of componentmonomers and polymers, including where such component monomers andpolymers are generally incompatible. Such processes, and the resultantcompositions, find use in various applications, for instance in themedical device field, such as ophthalmic devices and contact lenses.

In one aspect, therefore, the invention provides a polymer composition.The polymer composition is formed by a process comprising:

-   -   (a) providing a first reactive composition containing: (i) a        polymerization initiator that is capable, upon a first        activation, of forming two or more free radical groups, at least        one of which is further activatable by subsequent        activation; (ii) one or more ethylenically unsaturated        compounds; and (iii) a crosslinker;    -   (b) subjecting the first reactive composition to a first        activation step such that the first reactive composition        polymerizes therein to form a crosslinked substrate network        containing a covalently bound activatable free radical        initiator;    -   (c) combining the crosslinked substrate network with a second        reactive composition containing one or more ethylenically        unsaturated compounds; and    -   (d) activating the covalently bound activatable free radical        initiator of the crosslinked substrate network such that the        second reactive composition polymerizes therein with the        crosslinked substrate network to form a grafted polymeric        network and a byproduct polymer.

In a further aspect, the invention provides a process for making thepolymer composition.

In a yet further aspect, the invention provides a medical devicecomprising a polymer composition as described herein.

In a still further aspect, the invention provides an ophthalmic device,such as a contact lens, comprising a polymer composition as describedherein.

In still another aspect, the invention provides a crosslinked substratenetwork containing a covalently bound activatable free radical initiatorand that is a useful precursor for making the polymer compositionsdescribed herein. The crosslinked substrate network may be formed by aprocess comprising:

-   -   (a) providing a first reactive composition containing: (i) a        polymerization initiator that is capable, upon a first        activation, of forming two or more free radical groups, at least        one of which is further activatable by subsequent        activation; (ii) one or more ethylenically unsaturated        compounds; and (iii) a crosslinker; and    -   (b) subjecting the first reactive composition to a first        activation step such that the first reactive composition        polymerizes therein to form a crosslinked substrate network        containing a covalently bound activatable free radical        initiator.

In a further aspect, the invention provides a process for making acrosslinked substrate network.

DETAILED DESCRIPTION OF THE INVENTION

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention belongs. All publications, patentapplications, patents, and other references mentioned herein areincorporated by reference.

Unless otherwise indicated, numeric ranges, for instance as in “from 2to 10” or as in “between 2 and 10” are inclusive of the numbers definingthe range (e.g., 2 and 10).

Unless otherwise indicated, ratios, percentages, parts, and the like areby weight.

The phrase “number average molecular weight” refers to the numberaverage molecular weight (M_(n)) of a sample; the phrase “weight averagemolecular weight” refers to the weight average molecular weight (M_(w))of a sample; the phrase “polydispersity index” (PDI) refers to the ratioof M_(w) divided by M_(n) and describes the molecular weightdistribution of a sample. If the type of “molecular weight” is notindicated or is not apparent from the context, then it is intended torefer to number average molecular weight.

As used herein, the term “about” refers to a range of +/−10 percent ofthe number that is being modified. For example, the phrase “about 10”would include both 9 and 11.

As used herein, the term “(meth)” designates optional methylsubstitution. Thus, a term such as “(meth)acrylate” denotes bothmethacrylate and acrylate.

Wherever chemical structures are given, it should be appreciated thatalternatives disclosed for the substituents on the structure may becombined in any combination. Thus, if a structure contained substituentsR* and R**, each of which contained three lists of potential groups, 9combinations are disclosed. The same applies for combinations ofproperties.

The average number of repeating units in a polymer sample is known asits “degree of polymerization.” When a generic chemical formula of apolymer sample, such as [***]n is used, “n” refers to its degree ofpolymerization, and the formula shall be interpreted to represent thenumber average molecular weight of the polymer sample.

As used herein, the term “individual” includes humans and vertebrates.

As used herein, the term “medical device” refers to any article that isdesigned to be used while either in or on mammalian tissues or fluids,and preferably in or on human tissue or fluids. Examples of thesedevices include but are not limited to wound dressings, sealants, tissuefillers, drug delivery systems, coatings, adhesion prevention barriers,catheters, implants, stents, and ophthalmic devices such as intraocularlenses, corneal inlays, and contact lenses. The medical devices may beophthalmic devices, preferably contact lenses.

As used herein, the term “ophthalmic device” refers to any device whichresides in or on the eye or any part of the eye, including the ocularsurface. These devices can provide optical correction, cosmeticenhancement, vision enhancement, therapeutic benefit (for example asbandages) or delivery of active components such as pharmaceutical andnutraceutical components, or a combination of any of the foregoing.Examples of ophthalmic devices include but are not limited to lenses,optical and ocular inserts, including but not limited to punctal plugs,and the like. “Lenses” include soft contact lenses, hard contact lenses,hybrid contact lenses, intraocular lenses, and inlay and overlay lenses.The ophthalmic device preferably may comprise a contact lens.

As used herein, the term “contact lens” refers to an ophthalmic devicethat can be placed on the cornea of an individual's eye. The contactlens may provide corrective, cosmetic, or therapeutic benefit, includingwound healing, the delivery of drugs or nutraceuticals, diagnosticevaluation or monitoring, ultraviolet light blocking, visible light orglare reduction, or any combination thereof. A contact lens can be ofany appropriate material known in the art and can be a soft lens, a hardlens, or a hybrid lens containing at least two distinct portions withdifferent physical, mechanical, or optical properties, such as modulus,water content, light transmission, or combinations thereof.

The medical devices, ophthalmic devices, and lenses of the invention maybe comprised of silicone hydrogels. These silicone hydrogels typicallycontain at least one hydrophilic monomer and at least onesilicone-containing component that are covalently bound to one anotherin the cured device. The medical devices, ophthalmic devices, and lensesof the invention may also be comprised of conventional hydrogels, orcombination of conventional and silicone hydrogels.

A “macromolecule” is an organic compound having a number averagemolecular weight of greater than 1500, and may be reactive ornon-reactive.

As used herein, the “target macromolecule” is the intended macromoleculebeing synthesized from the reactive composition comprising monomers,macromers, prepolymers, cross-linkers, initiators, additives, diluents,and the like.

As used herein, a “monomer” is a mono-functional molecule which canundergo chain growth polymerization, and in particular, free radicalpolymerization, thereby creating a repeating unit in the chemicalstructure of the target macromolecule. Some monomers have di-functionalimpurities that can act as cross-linking agents. A “hydrophilic monomer”is also a monomer which yields a clear single phase solution when mixedwith deionized water at 25° C. at a concentration of 5 weight percent. A“hydrophilic component” is a monomer, macromer, prepolymer, initiator,cross-linker, additive, or polymer which yields a clear single phasesolution when mixed with deionized water at 25° C. at a concentration of5 weight percent.

As used herein, a “macromonomer” or “macromer” is a linear or branchedmacromolecule having at least one reactive group that can undergo chaingrowth polymerization, and in particular, free radical polymerization.

As used herein, the term “polymerizable” means that the compoundcomprises at least one reactive group which can undergo chain growthpolymerization, and in particular, free radical polymerization. Thus,“reactive group” refers to a free radical reactive group, non-limitingexamples of which include, without limitation, (meth)acrylates,(meth)acrylamides, styrenes, vinyls, vinyl ethers, N-vinyllactams,N-vinylamides, O-vinylcarbamates, O-vinylcarbonates, O-vinylethers, andother vinyl groups. In one embodiment, the free radical reactive groupscomprise acrylate, methacrylate, acrylamide, methacrylamide, N-vinyllactam, N-vinylamide, styryl functional groups, and mixtures thereof. Incontrast, the term “non-polymerizable” means that the compound does notcomprise such a free radical reactive group.

Examples of the foregoing include substituted or unsubstitutedC₁₋₆alkyl(meth)acrylates, C₁₋₆alkyl(meth)acrylamides, C₂₋₁₂alkenyls,C₂₋₁₂alkenylphenyls, C₂₋₁₂alkenylnaphthyls, C₂₋₆alkenylphenylC₁₋₆alkyls,where suitable substituents on said C₁₋₆ alkyls include ethers,hydroxyls, carboxyls, halogens and combinations thereof.

Any type of free radical polymerization may be used including but notlimited to bulk, solution, suspension, and emulsion as well as any ofthe controlled radical polymerization methods such as stable freeradical polymerization, nitroxide-mediated living polymerization, atomtransfer radical polymerization, reversible addition fragmentation chaintransfer polymerization, organotellurium mediated living radicalpolymerization, and the like.

An “ethylenically unsaturated compound” is a monomer, macromer, orprepolymer that contains at least one reactive group. An ethylenicallyunsaturated compound may preferably consist of one reactive group.

As used herein, a “silicone-containing component” or “siliconecomponent” is a monomer, macromer, prepolymer, cross-linker, initiator,additive, or polymer in the reactive composition with at least onesilicon-oxygen bond, typically in the form of siloxy groups, siloxanegroups, carbosiloxane groups, and mixtures thereof. Examples ofsilicone-containing components which are useful in this invention may befound in U.S. Pat. Nos. 3,808,178, 4,120,570, 4,136,250, 4,153,641,4,740,533, 5,034,461, 5,070,215, 5,244,981, 5,314,960, 5,331,067,5,371,147, 5,760,100, 5,849,811, 5,962,548, 5,965,631, 5,998,498,6,367,929, 6,822,016, 6,943,203, 6,951,894, 7,052,131, 7,247,692,7,396,890, 7,461,937, 7,468,398, 7,538,146, 7,553,880, 7,572,841,7,666,921, 7,691,916, 7,786,185, 7,825,170, 7,915,323, 7,994,356,8,022,158, 8,163,206, 8,273,802, 8,399,538, 8,415,404, 8,420,711,8,450,387, 8,487,058, 8,568,626, 8,937,110, 8,937,111, 8,940,812,8,980,972, 9,056,878, 9,125,808, 9,140,825, 9,156,934, 9,170,349,9,217,813, 9,244,196, 9,244,197, 9,260,544, 9,297,928, 9,297,929, andEuropean Patent No. 080539. These patents are hereby incorporated byreference in their entireties.

A “polymer” is a target macromolecule composed of the repeating units ofthe monomers and macromers used during polymerization.

A “homopolymer” is a polymer made from one monomer; a “copolymer” is apolymer made from two or more monomers; a “terpolymer” is a polymer madefrom three monomers. A “block copolymer” is composed of compositionallydifferent blocks or segments. Diblock copolymers have two blocks.Triblock copolymers have three blocks. “Comb or graft copolymers” aremade from at least one macromer.

A “repeating unit” is the smallest group of atoms in a polymer thatcorresponds to the polymerization of a specific monomer or macromer.

An “initiator” is a molecule that can decompose into free radical groupswhich can react with a monomer to initiate a free radical polymerizationreaction. A thermal initiator decomposes at a certain rate depending onthe temperature; typical examples are azo compounds such as1,1′-azobisisobutyronitrile and 4,4′-aobis(4-cyanovaleric acid),peroxides such as benzoyl peroxide, tert-butyl peroxide, tert-butylhydroperoxide, tert-butyl peroxybenzoate, dicumyl peroxide, and lauroylperoxide, peracids such as peracetic acid and potassium persulfate aswell as various redox systems. A photo-initiator decomposes by aphotochemical process; typical examples are derivatives of benzil,benzoin, acetophenone, benzophenone, camphorquinone, and mixturesthereof as well as various monoacyl and bisacyl phosphine oxides andcombinations thereof.

A “free radical group” is a molecule that has an unpaired valenceelectron which can react with a reactive group to initiate a freeradical polymerization reaction.

A “cross-linking agent” or “crosslinker” is a di-functional ormulti-functional monomer which can undergo free radical polymerizationat two or more locations on the molecule, thereby creating branch pointsand a polymeric network. The two or more polymerizable functionalitieson the crosslinker may be the same or different and may, for instance,be independently selected from vinyl groups (including allyl),(meth)acrylate groups, and (meth)acrylamide groups. Common examples areethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate,trimethylolpropane trimethacrylate, methylene bisacrylamide, triallylcyanurate, and the like.

A “prepolymer” is a reaction product of monomers (or macromers) whichcontains remaining reactive groups capable of undergoing furtherreaction to form a polymer.

A “polymeric network” is a type of polymer that is in the form of across-linked macromolecule. Generally, a polymeric network may swell butcannot dissolve in solvents. For instance, the crosslinked substratenetwork of the invention is a material that is swellable, withoutdissolving.

“Hydrogels” are polymeric networks that swell in water or aqueoussolutions, typically absorbing at least 10 weight percent water (at 25°C.). “Silicone hydrogels” are hydrogels that are made from at least onesilicone-containing component with at least one hydrophilic component.Hydrophilic components may also include non-reactive polymers.

“Conventional hydrogels” refer to polymeric networks made from monomerswithout any siloxy, siloxane or carbosiloxane groups. Conventionalhydrogels are prepared from reactive compositions predominantlycontaining hydrophilic monomers, such as 2-hydroxyethyl methacrylate(“HEMA”), N-vinyl pyrrolidone (“NVP”), N, N-dimethylacrylamide (“DMA”)or vinyl acetate.

As used herein, the term “reactive composition” refers to a compositioncontaining one or more reactive components (and optionally non-reactivecomponents) which are mixed (when more than one is present) togetherand, when subjected to polymerization conditions, form polymercompositions. If more than one component is present, the reactivecomposition may also be referred to herein as a “reactive mixture” or a“reactive monomer mixture” (or RMM). The reactive composition comprisesreactive components such as the monomers, macromers, prepolymers,cross-linkers, and initiators, and optional additives such as wettingagents, release agents, dyes, light absorbing compounds such as UV-VISabsorbers, pigments, dyes and photochromic compounds, any of which maybe reactive or non-reactive but are preferably capable of being retainedwithin the resulting polymer composition, as well as pharmaceutical andnutraceutical compounds, and any diluents. It will be appreciated that awide range of additives may be added based upon the final product whichis made and its intended use. Concentrations of components of thereactive composition are expressed as weight percentages of allcomponents in the reaction composition, excluding diluent. When diluentsare used, their concentrations are expressed as weight percentages basedupon the amount of all components in the reaction composition and thediluent.

“Reactive components” are the components in the reactive compositionwhich become part of the chemical structure of the resulting material bycovalent bonding, hydrogen bonding, electrostatic interactions, theformation of interpenetrating polymeric networks, or any other means.

As used herein, the term “silicone hydrogel contact lens” refers to acontact lens comprising at least one silicone hydrogel. Siliconehydrogel contact lenses generally have increased oxygen permeabilitycompared to conventional hydrogels. Silicone hydrogel contact lenses useboth their water and polymer content to transmit oxygen to the eye.

As noted above, in one aspect, the invention provides a polymercomposition formed by a process comprising:

-   -   (a) providing a first reactive composition containing: (i) a        polymerization initiator that is capable, upon a first        activation, of forming two or more free radical groups, at least        one of which is further activatable by subsequent        activation; (ii) one or more ethylenically unsaturated        compounds; and (iii) a crosslinker;    -   (b) subjecting the first reactive composition to a first        activation step such that the first reactive composition        polymerizes therein to form a crosslinked substrate network        containing a covalently bound activatable free radical        initiator;    -   (c) combining the crosslinked substrate network with a second        reactive composition containing one or more ethylenically        unsaturated compounds; and    -   (d) activating the covalently bound activatable free radical        initiator of the crosslinked substrate network such that the        second reactive composition polymerizes therein with the        crosslinked substrate network to form a grafted polymeric        network and a byproduct polymer.

The polymerization initiator may be any composition with the ability togenerate free radical groups in two or more separate activation steps.There is no particular requirement in the invention with respect to whattype of polymerization initiator is used or the mechanism of activation,as long as the first activation and the second activation can beconducted sequentially. Thus, suitable polymerization initiators may,for example, be activated thermally, by visible light, by ultravioletlight, via electron beam irradiation, by gamma ray irradiation, orcombinations thereof. Examples of polymerization initiators for use inthe invention include, without limitation, bisacylphosphine oxides(“BAPO”), bis(acyl)phosphane oxides (e.g., bis(mesitoyl)phosphinicacid), azo compounds, peroxides, alpha-hydroxy ketones, alpha-alkoxyketones, 1, 2-diketones, germanium based compounds (such asbis(4-methoxybenzoyl)diethylgermanium), or combinations thereof.

BAPO initiators are preferred. Examples of suitable BAPO initiatorsinclude, without limitation, compounds having the chemical structure offormula I.

-   -   wherein Ar¹ and Ar² are independently substituted or        unsubstituted aryl groups, typically substituted phenyl groups,        wherein the substituents are linear, branched, or cyclic alkyl        groups, such as methyl groups, linear, branched, or cyclic        alkoxy groups, such as methoxy groups, and halogen atoms;        preferably Ar¹ and Ar² have identical chemical structures; and        wherein R¹ is a linear, branched, or cyclic alky group having        from 1 to 10 carbon atoms, or R¹ is a phenyl group, a hydroxyl        group, or an alkoxy group having from 1 to 10 carbon atoms.

It should be noted that polymerization initiators that are activatableby different types of energy for the initial and subsequent activationsmay be used. For instance, materials that undergo a first thermalactivation and a second activation via irradiation are within the scopeof the invention. Examples of such mixed activation materials includecompounds of formulae A-D:

-   -   wherein Ar¹ and Ar² are independently substituted or        unsubstituted aryl groups, typically substituted phenyl groups,        wherein the substituents are linear, branched, or cyclic alkyl        groups, such as methyl groups, linear, branched, or cyclic        alkoxy groups, such as methoxy groups, and halogen atoms;        preferably Ar¹ and Ar² have identical chemical structures; and        wherein R¹ is a linear, branched, or cyclic alkyl group having        from 1 to 10 carbon atoms; wherein R² is difunctional methylene        linking group that may further comprise ether, ketone, or ester        groups along the methylene chain having from 1 to 10 carbon        atoms; and R³ is a hydrogen atom, a hydroxyl group, or a linear,        branched, or cyclic alkoxy group having from 1 to 10 carbon        atoms. A further example is tert-butyl        7-methyl-7-(tert-butylazo)peroxyoctanoate.

Furthermore, diazo compounds, diperoxy compounds, or azo-peroxycompounds that exhibit two distinct decomposition temperatures may beused in the prevent invention.

Preferably, the polymerization initiator is a photopolymerizationinitiator, preferably a bisacylphosphine oxide. Bisacylphosphine oxidesare desirable because they can undergo sequential activations steps atdifferent wavelengths and are therefore simple to use. At the longerwavelength, bisacylphosphine oxides can form two free radical groups,one of which is a monoacylphosphine oxide. The monacylphosphine oxide(MAPO) can then undergo a second activation, typically at a shorterwavelength. A particularly preferred bisacylphosphine oxide isbis(2,4,6-trimethylbenzoyl) phenylphosphine oxide, for which the longerwavelength is typically above 420 nm (e.g., 435 nm and above) and theshorter wavelength is typically 420 nm and below. It may be preferableto use an LED or equivalent light in which the bandwidths are relativelynarrow as the radiation source, thereby allowing initial irradiationwhile preserving some or most of the MAPO groups in the crosslinkedsubstrate network.

Other exemplary bisacylphosphine oxide compounds that may be usedinclude bis-(2,6-dimethoxybenzoyl)-2,4,4-trimethylpenthylphosphineoxide, bis(2,4,6-trimethylbenzoyl)-2,4,4-trimethylpenthylphosphineoxide, or bis(2,4,6-trimethylbenzoyl)phosphinic acid or salt thereof.

In the invention, the first reactive composition, which contains thepolymerization initiator, one or more ethylenically unsaturatedcompounds, and a crosslinker, is subjected to a first activation stepunder conditions that cause the polymerization initiator to undergo itsinitial activation. For example, if the polymerization initiator is aBAPO, the first reactive composition may be irradiated at 435 nm orabove using an appropriate light source. The first reactive compositionconsequently polymerizes to form a crosslinked substrate network. Thecrosslinked substrate network contains the residue of the polymerizationinitiator as a covalently bound activatable free radical initiator.

The activation and polymerization of the first reactive composition maybe carried out using techniques known to those skilled in the art. Forexample, the reactive components of the first reactive composition maybe mixed in a vessel. A diluent may optionally be used to facilitate themixing. The mixture may be filtered, degassed, and heated to a desiredtemperature and then irradiated under conditions to cause a firstactivation of the polymerization initiator and consequent formation ofthe crosslinked substrate network. The vessel for the polymerization maybe a mold, for instance where it is desired for the product to have aspecific shape.

According to the invention, the crosslinked substrate network describedabove is combined with a second reactive composition, containing one ormore ethylenically unsaturated compounds. The crosslinked substratenetwork is a swellable material and therefore absorbs some reactivecomponents for the subsequent grafting reaction. Absorption into thecrosslinked substrate network may be carried out in various ways. Forinstance, the crosslinked substrate network may be placed in the secondreactive composition and allowed to swell. Or the crosslinked substratenetwork may be first swollen in a solvent and then combined with thesecond reactive composition, e.g., by suspending the pre-swollencrosslinked substrate network in the second reactive composition, duringwhich the reactive components partition into the crosslinked substratenetwork by molecular diffusion and fluid exchange prior. There is noparticular minimum amount of reactive components that should absorb intothe crosslinked substrate network as long as some is present (greaterthan 0 weight percent of reactive components). In some embodiments, itmay be preferable for the crosslinked substrate network to be swellablein the second reactive composition by at least 0.0001 weight percent,alternatively at least 0.01 weight percent, alternatively at least 0.1weight percent, alternatively at least 5 weight percent, alternativelyat least 10 weight percent, or alternatively at least 25 weight percent,at 25° C., relative to its dry weight.

Following the mixing of the crosslinked substrate network with thesecond reactive composition, the activatable free radical initiator ofthe crosslinked substrate network is activated. For example, if thepolymerization initiator used in step (a) of the process is a BAPO, thenthe free radical initiator covalently bound to the crosslinked substratenetwork (in this example, a monoacylphosphine oxide) may be activated byirradiation at 420 nm or below using an appropriate light source. Thesecond reactive composition then undergoes polymerization, andcovalently grafts with the crosslinked substrate network via the freeradical initiator in the substrate. The product is thus a graftedpolymeric network.

It should be noted that the free radical initiator covalently bound tothe crosslinked substrate network forms two free radical groups whenactivated, one of which may not be covalently bound to the substrate.Consequently, some of the reactive components in the second reactivecomposition may polymerize via the unbound free radical group to form apolymer that is not covalently bound with the network. Such polymer isreferred to herein as a “byproduct polymer.” This byproduct polymer maybe induced to covalently bind with the grafted polymeric network byinclusion of a crosslinking agent in the second reactive composition.The composition may contain at least a portion of the byproduct polymerthat is not covalently bound to the grafted polymeric network. Toachieve this, the polymerization of the second reactive composition isconducted in the substantial absence of a crosslinker. By “substantialabsence of a crosslinker” is meant that any crosslinker used in thesecond reactive composition is present in less than a stoichiometricamount. In some embodiments, no crosslinker is present in the secondreactive composition.

The activation and polymerization of the second reactive composition andthe crosslinked substrate network may, for example, be carried out bymixing the reactive components and the substrate in a vessel. A diluentmay optionally be used to facilitate the mixing and to help swell thesubstrate (e.g., if it is not already swollen or hydrated). The mixturemay be degassed, heated, equilibrated, and irradiated under conditionsto cause activation of the covalently bound activatable free radicalinitiator.

The first and second reactive compositions of the invention containethylenically unsaturated compounds as reactive components. Theethylenically unsaturated compounds undergo polymerization to form thepolymer compositions described herein. As will be appreciated, a widevariety of ethylenically unsaturated compounds may be used in theinvention.

The ethylenically unsaturated compounds may be the same or differentbetween the first reactive composition and the second reactivecomposition, although in some embodiments, it is preferable that atleast some of the ethylenically unsaturated compounds in eachcomposition are different. By using materials for the first reactivecomposition that are different from the second reactive composition, itbecomes possible to design interpenetrating networks and graft articlesthat combine desirable properties from materials that may otherwise notbe readily compatible. This is one of the advantages of the invention.

The ethylenically unsaturated compound for inclusion in the firstreactive composition and/or the second reactive composition may comprisean independently selected silicone-containing component.

The silicone-containing component may be a monomer or macromer and maycomprise at least one reactive group and at least one siloxane group.The silicone-containing components may have at least four repeatingsiloxane units, which may be any of the groups defined below.

The silicone-containing component may also contain at least one fluorineatom. The silicone-containing component may be selected from thepolydisubstituted siloxane macromer of Formula II,

-   -   wherein at least one R⁴ is a reactive group, and the remaining        R⁴ are independently selected from reactive groups, monovalent        alkyl groups, or monovalent aryl groups, any of the foregoing        which may further comprise functionality selected from hydroxy,        amino, oxa, carboxy, alkyl carboxy, alkoxy, amido, carbamate,        carbonate, halogen or combinations thereof; fluoroalkyl alkyl or        aryl groups; partially fluorinated alkyl or aryl groups;        halogens; linear, branched or cyclic alkoxy or aryloxy groups;        linear or branched polyethyleneoxyalkyl groups,        polypropyleneoxyalkyl groups, or        poly(ethyleneoxy-co-propyleneoxyalkyl groups; and monovalent        siloxane chains comprising between 1-100 siloxane repeat units        which may further comprise functionality selected from alkyl,        alkoxy, hydroxy, amino, oxa, carboxy, alkyl carboxy, alkoxy,        amido, carbamate, halogen or combinations thereof,    -   wherein n is 0 to 500 or 0 to 200, or 0 to 100, or 0 to 20,        where it is understood that when n is other than 0, n is a        distribution having a mode equal to a stated value.

In Formula II from one to three R⁴ may comprise reactive groups.Suitable monovalent alkyl and aryl groups include unsubstituted andsubstituted monovalent linear, branched or cyclic C₁ to C₁₆ alkylgroups, or unsubstituted monovalent C₁ to C₆ alkyl groups, such assubstituted and unsubstituted methyl, ethyl, propyl, butyl; substitutedor unsubstituted C₆-C₁₄ aryl groups, or a substituted or un-substitutedC₆ aryl group, wherein the substituents include amido, ether, amino,halo, hydroxyl, carboxyl, carbonyl groups; or a phenyl or benzyl group,combinations thereof and the like.

When one R⁴ is a reactive group, the silicone containing compounds maybe selected from the polydisubstituted siloxane macromer of FormulaeIIIa or IIIb; the styryl polydisubstituted siloxane macromer of FormulaIVa or IVb or the carbosilane of Formula IVc:

-   -   wherein R⁵ is a hydrogen atom or methyl; wherein Z is selected        from O, N, S or NCH₂CH₂O; when Z=O or S, R⁶ is not required;        wherein R⁶ is H or a linear, branched, or cyclic alkyl group        containing one to eight carbon atoms, any of which may be        further substituted with at least one hydroxy group, and which        may be optionally substituted with amide, ether, and        combinations thereof, wherein j is a whole number between 1 and        20; q is up to 50, 5 to 30 or 10-25; and n¹ and n² are between 4        to 100; 4 to 50; or 4 to 25; n³ is 1-50, 1-20, or 1-10; wherein        R⁷ is a substituted or unsubstituted C₁₋₆, C₁₋₄ or C₂₋₄ alkylene        segment (CH₂)_(r), each methylene group may optionally be        independently substituted with ethers, amines, carbonyls,        carboxylates, carbamates and combinations thereof, or an        oxyalkylene segment (OCH₂)_(k) and k is a whole number from one        to three, or wherein R⁷ may be a mixture of alkylene and        oxyalkylene segments and the sum of r and k is between 1 and 9;        wherein each R⁸ and R⁹ are independently a linear, branched, or        cyclic alkyl group containing between one and six carbon atoms,        a linear, branched, or cyclic alkoxy group containing between        one and six carbon atoms, a linear or branched        polyethyleneoxyalkyl group, a phenyl group, a benzyl group, a        substituted or un-substituted aryl group, a fluoroalkyl group, a        partially fluorinated alkyl group, a perfluoroalkyl group, a        fluorine atom, or combinations thereof, and wherein R¹⁰ is a        substituted or un-substituted linear or branched alkyl group        having 1 to eight carbon atoms, or 1 to 4 carbon atoms, or        methyl or butyl; or an aryl group, any of which may be        substituted with one or more fluorine atoms.

Non-limiting examples of polysiloxane macromers includemono-methacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxanes (mPDMS) as shown in Formula V wherein n is between3 and 15; mono-methacryloxypropyl terminated mono-n-alkyl terminatedpolydimethylsiloxanes as shown in Formula VIa wherein n is between4-100, 4 and 20, or between 3 and 15; mono-n-alkyl terminated,polydimethyl-co-polyethylene glycol siloxanes as shown in Formula VIbwherein n¹ and n² are between 4 to 100; 4 to 50; or 4 to 25; n³ is 1-50,1-20, or 1-10; and R⁵ through R¹⁰ are as defined as in Formula IIIa; andmacromers having the chemical structures as shown in Formulae VIIathrough Xb, wherein n is between 4-100, 4 and 20, or between 3 and 15;R⁵ and R⁶ are defined as in Formula IIIa; and R¹⁰ may be C₁-C₄ alkyl ormethyl or butyl.

Examples of suitable mono(meth)acryloxyalkylpolydisubstituted siloxanesinclude mono(meth)acryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxane, mono(meth)acryloxypropyl terminated mono-n-methylterminated polydimethylsiloxane, mono(meth)acryloxypropyl terminatedmono-n-butyl terminated polydiethylsiloxane, mono(meth)acryloxypropylterminated mono-n-methyl terminated polydiethylsiloxane,mono(meth)acrylamidoalkylpolydialkylsiloxanes mono(meth)acryloxyalkylterminated mono-alkyl polydiarylsiloxanes, and mixtures thereof.

In Formula II, when n is zero, one or more R⁴ may comprise a reactivegroup, two or more R⁴ comprise tristriC₁₋₄alkylsiloxysilane groups,monovalent siloxane chains comprising between 1-100, 1-10 or 1-5siloxane repeat units which may further comprise functionality selectedfrom alkyl, alkoxy, hydroxy, amino, oxa, carboxy, alkyl carboxy, alkoxy,amido, carbamate, halogen or combinations thereof; and the remaining R⁴are selected from monovalent alkyl groups having 1 to 16, 1 to 6 or 1-4carbon atoms. Non-limiting examples of silicone components include,3-methacryloxypropyltris(trimethylsiloxy)silane (TRIS),3-methacryloxypropylbis(trimethylsiloxy)methylsilane, and3-methacryloxypropylpentamethyl disiloxane.

The number of siloxane repeating units, n, may also be 2 to 50, 3 to 25,or 3 to 15; wherein at least one terminal R⁴ comprises a reactive groupand the remaining R⁴ are selected from monovalent alkyl groups having 1to 16 carbon atoms, or from monovalent alkyl groups having 1 to 6 carbonatoms. Silicone-containing compounds may also include those where n is 3to 15, one terminal R⁴ comprises a reactive group, the other terminal R⁴comprises a monovalent alkyl group having 1 to 6 carbon atoms and theremaining R⁴ comprise monovalent alkyl group having 1 to 3 carbon atoms.Non-limiting examples of silicone components includemonomethacryloxypropyl n-butyl terminated polydimethylsiloxanes(M_(n)=800-1000), (mPDMS, as shown in Formula V).

Formula II may also include compounds where n is 5 to 400 or from 10 to300, both terminal R⁴ comprise reactive groups and the remaining R⁴ areindependently of one another selected from monovalent alkyl groupshaving 1 to 18 carbon atoms which may have ether linkages between carbonatoms and may further comprise halogen.

One to four R⁴ in Formula II may comprise a vinyl carbonate or vinylcarbamate of Formula XI:

-   -   wherein: Y denotes O—, S— or NH—; R⁵ denotes a hydrogen atom or        methyl.

The silicone-containing vinyl carbonate or vinyl carbamate monomersspecifically include:1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(vinyloxycarbonylthio) propyl-[tris (trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl] propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl] propyl vinyl carbamate;trimethylsilylethyl vinyl carbonate; trimethylsilylmethyl vinylcarbonate, and the crosslinking agent of Formula XII.

Where materials with moduli below about 200 psi are desired, only one R⁴comprises a reactive group and no more than two of the remaining R⁴groups comprise monovalent siloxane groups.

Another suitable silicone-containing component is compound of FormulaXIII in which the sum of x and y is a number in the range of 10 to 30.The silicone containing component of Formula XXIII is formed by thereaction of fluoroether, hydroxy-terminated polydimethylsiloxane,isophorone diisocyanate and isocyanatoethylmethacrylate.

A silicone-containing component may be selected from acrylamidesilicones of U.S. Pat. No. 8,415,405. Other silicone components suitablefor use in this invention include those described in WO 96/31792 such asmacromers containing polysiloxane, polyalkylene ether, diisocyanate,polyfluorinated hydrocarbon, polyfluorinated ether and polysaccharidegroups. Another class of suitable silicone-containing componentsincludes silicone-containing macromers made via Group TransferPolymerization (GTP), such as those disclosed in U.S. Pat. Nos.5,314,960, 5,331,067, 5,244,981, 5,371,147, and 6,367,929. U.S. Pat.Nos. 5,321,108, 5,387,662, and 5,539,016 describe polysiloxanes with apolar fluorinated graft or side group having a hydrogen atom attached toa terminal difluoro-substituted carbon atom. US 2002/0016383 describeshydrophilic siloxanyl methacrylates containing ether and siloxanyllinkages and crosslinkable monomers containing polyether andpolysiloxanyl groups. Any of the foregoing polysiloxanes can also beused as the silicone-containing component in this invention.

A silicone component may be selected from the group consisting ofmonomethacryloxypropyl terminated, mono-n-alkyl terminated linearpolydisubstituted siloxane; methacryloxypropyl-terminated linearpolydisubstituted siloxane; and mixtures thereof.

A containing silicone component may also be selected frommonomethacrylate terminated, C₁-C₄ alkyl terminated, linearpolydimethylsiloxanes; and mixtures thereof.

Further examples include those selected from Formula VIa where R¹⁰ ismethyl or butyl, compounds of Formulae V-Xb, and the macromers shown inFormula XIV or XV where n is 1-50 and m is 1-50, 1-20 or 1-10:

Further examples of silicone-containing components include mPDMS ofFormula VIa, compounds of Formulae VIIa or b, or VIII where R⁵ is methyland R¹⁰ is selected from methyl or butyl, and the macromers shown inFormula XIV where n is 1-50 or 4-40, 4-20.

Specific examples of silicone containing components that contain morethan one reactive group include bismethacryloxypropylpolydimethylsiloxane, where n may be 4-200, or 4-150, and the followingcompounds of Formula XVIa-XVIIc, where n¹ and n² are independentlyselected from 4 to 100; 4 to 50; or 4 to 25; n³ is 1-50, 1-20 or 1-10, mis 1-100, 1-50, 1-20 or 1-10, q is up to 50, 5-30 or 10-25; s is up to50, 5-30 or 10-25; and Z, R⁵, R⁶, R⁸ and R⁹ are defined as in FormulaIIIa.

A silicone component may have an average molecular weight of from about400 to about 4000 Daltons.

When Z is O, the silicone containing component may be amono-methacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxanes (mPDMS) as shown in Formula V wherein n is between3 and 15; mono-methacryloxypropyl terminated mono-n-alkyl terminatedpolydimethylsiloxanes as shown in Formula VIa wherein n is between 3 and15 and R¹⁰ is a linear, branched, or cyclic alkyl group containingbetween 1 and 8 carbon atoms; and macromers having the chemicalstructures as shown in Formulae VIIa through XIIc, or VIII where n isbetween 4 and 20, or between 3-30, 3-25, 3-20 or 3-15.

When Z is N, further examples of polysiloxane silicone-containingcomponents include mono(meth)acrylamidoalkylpolydialkylsiloxanes and maybe selected from those disclosed in U.S. Pat. No. 8,415,405, and thoseshown in Formulae XIII wherein R⁵, R⁶, R¹, R⁹, R¹⁰ are defined as inFormula IIIa, mono(meth)acrylamidoalkyl polydimethylsiloxanes, such asthose in Formulae XIX-XXIII, and N-(2,3-dihydroxypropane)-N′-(propyltetra(dimethylsiloxy) dimethylbutylsilane)acrylamide:

Examples of styryl monomers include tris(trimethylsiloxy)silyl styrene.Examples of styryl macromers are shown below in chemical Formulae XXIVthrough XIX, wherein n is between 4 and 20, or between 3-30, 3-25, 3-20or 3-15.

The length of the silicone chain may have an impact on the modulus ofthe resulting silicone material and may be adjusted along with the othercomponents of the reactive composition to achieve the desired balance ofphysical and mechanical properties. For instance, the length of thesilicone chain may be chosen to attain a water content for a siliconehydrogel that moderates stiffness and increases elongation to breakconcurrently. As the polydialkylsiloxane chain length increases, moduluswill decrease and elongation to break will increase. Polydialkylsiloxanechain lengths between 1 and 20, 1 and 15, 3-30, 3-25, 3-20 or 3-15 maybe selected.

The silicone-containing component may further includesilicone-containing monomers with branched siloxane groups. Examplesinclude tris(trimethylsiloxy)silylstyrene (Styryl-TRIS),3-tris(trimethylsiloxy)silylpropyl methacrylate (TRIS),N-[3-tris(trimethylsiloxy)silyl]-propyl acrylamide (TRIS-Am),2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propylmethacrylate (SiMAA), and other bulky silicone monomers, such as thosein Formulae XXa through XXe, wherein R¹¹ is independently linear,branched, or cyclic alkyl groups containing between one and eight carbonatoms, or are trimethylsiloxy groups.

The aforementioned macromers have methacrylate, acrylamide, ormethacrylamide reactive groups. These reactive groups may be replacedwith any other reactive group capable of undergoing free radicalpolymerization, such as acrylates, styrenes, vinyl ethers,N-vinyllactams, N-vinylamides, N-vinylimides, N-vinylureas,O-vinylcarbamates, O-vinylcarbonates, and other vinyl compounds. Wheremoduli greater than about 5000 psi are desired, monomers and macromerswith styryl reactive groups are beneficially included.

Alternative silicone-containing components suitable for use includethose described in WO 96/31792 and U.S. Pat. Nos. 5,314,960, 5,331,067,5,244,981, 5,371,147, 6,367,929, 5,321,108, 5,387,662, 5,539,016,6,867,245, and others will be apparent to one skilled in the art

The silicone containing component may also comprise one or morehydroxyl-containing silicone component. Hydroxyl-containing siliconecomponents may help to compatibilize high concentrations of siliconecontaining components with hydrophilic components, including polymerichydrophilic components, and silicone components having bulky siloxanegroups or longer chains of repeating siloxane units. Hydroxyl-containingsilicone components include hydroxyl containing silicone monomers andmacromers. The hydroxyl-containing silicone components may have 4 to200, 4-100 or 4-20 siloxane repeating units and may be monofunctional ormultifunctional.

Hydroxyl-containing silicone components having 4 polydisubstitutedsiloxane repeating units in the siloxane chain are not a distributionand have four repeating units in each monomer. For allhydroxyl-containing silicone components having more than fourpolydisubstituted siloxane repeating units in the siloxane chain thenumber of repeating units is a distribution, with the peak of thedistribution centered around the listed number of repeat units.

Examples of hydroxyl-containing silicone monomers include propenoicacid-2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]-1-disiloxanyl]propoxy]propylester (SiMAA or SiGMA), and2-hydroxy-3-methacryloxypropyloxypropyl-tris(trimethylsiloxy)silane, andcompounds of Formula XXd.

The hydroxyl-containing silicone components may be selected frommonofunctional hydroxyl substituted poly(disubstituted siloxane)s ofFormula XXI:

-   -   wherein Z is selected from O, N, S or NCH₂CH₂O, when Z is O or S        R⁶ is not present; R⁵ is independently H or methyl;    -   R⁶ is H or a linear, branched, or cyclic alkyl group containing        one to eight carbon atoms, any of which may be further        substituted with at least one hydroxy group, and which may be        optionally substituted with amide, ether, and combinations        thereof; R¹³ and R¹⁴ are independently a linear, branched, or        cyclic alkyl group containing one to eight carbon atoms, any of        which may be further substituted with at least one hydroxy        group, and which may be optionally substituted with amide,        ether, and combinations thereof; R³ and R⁴ may be independently        selected from methyl, ethyl or phenyl, or may be methyl; n is        the number of siloxane units and is from 4-100, 4-30, 4-15, and        4-8; and R¹⁵ is selected from straight or branched C₁ to C₈        alkyl groups, which may be optionally substituted with one or        more hydroxyl, amide, ether, and combinations thereof. R¹⁵ may        be straight or branched C₄ alkyl, either of which may optionally        be substituted with hydroxyl, or may be methyl.

Examples of monofunctional hydroxyl containing silicone componentsinclude mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminatedmono-n-butyl terminated polydimethylsiloxanes (OH-mPDMS) as shown inFormula XXIIa wherein n is between 4 and 30, 4-8 or 10-20; andpolydimethylsiloxanes having the chemical structures as shown inFormulae XXIIb through XXIIId, where n is between 4 and 30, 4 and 8 or10 and 20; n¹ n², and n³ are independently between 4 to 100; 4 to 50; 4to 25; R⁵, R¹², and R¹⁵ as defined in Formula XXI; R¹⁵ may also beselected from straight or branched C₁ to C₈ alkyl groups, which may beoptionally substituted with one or more hydroxyl, amide, ether,polyhydroxyl groups selected from straight or branched C₁ to C₈ groupshaving a formula of C_(f)H_(g)(OH)_(h) wherein f=1-8 and g+h=2f+1 andcyclic C₁ to C₈ groups having a formula of C_(f)H_(g)(OH)_(h) whereinf=1-8 and g+h=2f−1, and combinations thereof, or R⁵ may be selected frommethyl, butyl or hydroxyl substituted C₂-C₅ alkyl, including hydroxylethyl, hydroxyl propyl, hydroxyl butyl, hydroxyl pentyl and2,3-dihydroxypropyl; and polycarbosiloxanes of Formulae XXIVa-b where ais between 4-100 or 4-8; and Z, R⁵, R¹², R¹³, R¹⁴, and R¹⁵ are asdefined as in Formula XXI.

The hydroxyl-containing silicone component may also be selected frommultifunctional hydroxyl substituted, poly(disubstituted siloxane) ofFormula XXV having 10 to 500, or 10 to 200, or 10 to 100 siloxanerepeating units, and mixtures thereof:

-   -   wherein in Formula XXV, Z is selected from O, N, S or NCH₂CH₂O;        for Z=O and S, R¹⁶ is not required; R⁵ is independently a        hydrogen atom or methyl group;    -   R¹⁶ is H or a linear, branched, or cyclic alkyl group containing        one to eight carbon atoms, any of which may be further        substituted with at least one hydroxy group, and which may be        optionally substituted with amide, ether, and combinations        thereof R¹⁷, R¹⁸, R¹⁹, R²⁰, and R²¹ are independently selected        from the group consisting of a hydrogen atom or any of the        substituents defined for R²² and R²³; R²² and R²³ are        independently selected from the group consisting of a linear,        branched, or cyclic alkyl group containing one to eight carbon        atoms, any of which may be further substituted with at least one        hydroxy group, amido, ether, amino, carboxyl, carbonyl groups        and combinations; a linear or branched alkyleneoxy group,        specifically ethyleneoxy groups, [CH₂CH₂O]_(p) wherein p is        between 1 and 200, or 1 and 100, or 1 and 50, or 1 and 25, or 1        and 20, optionally substituted with one or more hydroxyl, amino,        amido, ether, carbonyl, carboxyl, and combinations thereof, a        C₁-C₆ linear or branched fluoroalkyl groups optionally        substituted with one or more hydroxyl, amino, amido, ether,        carbonyl, carboxyl, and combinations thereof, a substituted or        un-substituted aryl groups, specifically phenyl groups, wherein        the substituents are selected from halogen, hydroxyl, alkoxy,        alkylcarbonyl, carboxy, and linear or branched or cyclic alkyl        groups which may be further substituted with halogen, hydroxyl,        alkoxy, alkylcarbonyl, and carboxyl groups, and combinations        thereof, a, b, c, x, y and z are independently between 0 and        100, between 0 and 50, between 0 and 20, between 0 and 10, or        between 0 and 5; and may be ordered in any molecular sequence to        make a wide range of substituted hydroxy-oxa-alkylene chains;        and n is the number of siloxane repeating units and is from 10        to 500; 10 to 200; 10 to 100; 10 to 50; 10 to 20.

Examples of multifunctional hydroxyl containing silicones includeα-(2-hydroxy-1-methacryloxypropyloxypropyl)-ω-butyl-decamethylpentasiloxaneand the difunctional polysiloxanes of Formulae XXVI or XXVII, whereinthe substituents are defined as in Formula XXV and n¹ n², and n³ areindependently between 4 to 100; 4 to 50; 4 to 25:

Another example is the difunctional polysiloxanes shown in FormulaXXXVIII:

-   -   wherein R⁵ is independently a hydrogen atom or methyl group; R²⁴        and R²⁵ are independently a linear, branched, or cyclic alkyl        group containing one to eight carbon atoms, any of which may be        further substituted with at least one hydroxy group, amido,        ether, amino, carboxyl, carbonyl groups and combinations        thereof, or are independently selected from unsubstituted C₁₋₄        alkyl groups and C₁₋₄ alkyl groups substituted with hydroxyl or        ether; or are selected from methyl, ethyl or —(CH₂CH₂O)_(m)OCH₃        where m is 1-50, 1-20 and 1-10.

Further examples of silicone containing components for use in theinvention include materials of formula XXIX:

wherein

-   -   R⁵ is hydrogen or methyl;    -   Z¹ is O or N(R^(A9));    -   L¹ is alkylene containing 1 to 8 carbon atoms, or oxaalkylene        containing 3 to 10 carbon atoms, wherein L¹ is optionally        substituted with hydroxyl;    -   j2 is from 0 to 220, preferably from 1 to 220;    -   R^(A3), R^(A4), R^(A5), and R^(A7) are independently at each        occurrence C₁-C₆ alkyl, C₃-C₁₂ cycloalkyl, C₁-C₆ alkoxy, C₄-C₁₂        cyclic alkoxy, alkoxy-alkyleneoxy-alkyl, aryl (e.g., phenyl),        aryl-alkyl (e.g., benzyl), haloalkyl (e.g., partially or fully        fluorinated alkyl), siloxy, fluoro, or combinations thereof,        wherein each alkyl in the foregoing groups is optionally        substituted with one or more hydroxy, amino, amido, oxa,        carboxy, alkyl carboxy, carbonyl, alkoxy, carbamate, carbonate,        halo, phenyl, or benzyl, each cycloalkyl is optionally        substituted with one or more alkyl, hydroxy, amino, amido, oxa,        carbonyl, alkoxy, carbamate, carbonate, halo, phenyl, or benzyl        and each aryl is optionally substituted with one or more alkyl,        hydroxy, amino, amido, oxa, carboxy, alkyl carboxy, carbonyl,        alkoxy, carbamate, carbonate, halo, phenyl, or benzyl;    -   R^(A6) is siloxy, C₁-C₈ alkyl (e.g., C₁-C₄ alkyl, or butyl, or        methyl), or aryl (e.g., phenyl), wherein alkyl and aryl may        optionally be substituted with one or more fluorine atoms; and    -   R^(A9) is H, C₁-C₈ alkyl (preferably C₁-C₄ alkyl, such as        n-butyl, n-propyl, methyl or ethyl), or C₃-C₈ cycloalkyl        (preferably C₅-C₆ cycloalkyl), wherein alkyl and cycloalkyl are        optionally substituted with one or more groups independently        selected from hydroxyl, amide, ether, silyl (e.g.,        trimethylsilyl), siloxy (e.g., trimethylsiloxy), alkyl-siloxanyl        (where alkyl is itself optionally substituted with fluoro),        aryl-siloxanyl (where aryl is itself optionally substituted with        fluoro), and silyl-oxaalkylene- (where the oxaalkylene is itself        optionally substituted with hydroxyl).

Preferred compounds of formula XXIX include those wherein L¹ is C₂-C₅alkylene optionally substituted with hydroxyl. Preferably L¹ isn-propylene optionally substituted with hydroxyl.

Preferred compounds of formula XXIX include those wherein L¹ isoxaalkylene containing 4 to 8 carbon atoms optionally substituted withhydroxyl. Preferably L¹ is oxaalkylene containing five or six carbonatoms optionally substituted with hydroxyl. Examples include—(CH₂)₂—O—(CH₂)₃—, and —CH₂CH(OH)CH₂—O—(CH₂)₃—.

Preferred compounds of formula XXIX include those wherein Z¹ is O.

Preferred compounds of formula XXIX include those wherein Z¹ isN(R^(A9)), and R^(A9) is H.

Preferred compounds of formula XXIX include those wherein Z¹ isN(R^(A9)), and R^(A9) is C₁-C₄ alkyl optionally substituted with 1 or 2substituents selected from hydroxyl, siloxy, and C₁-C₆ alkyl-siloxanyl-(e.g., alkyl-[Si(R^(A3))(R^(A4))—O]_(n)—, where n is 1 or more).

Preferred compounds of formula XXIX include those wherein j2 is 1.

Preferred compounds of formula XXIX include those wherein j2 is from 2to 220, or from 2 to 100, or from 10 to 100, or from 24 to 100, or from4 to 20, or from 4 to 10.

Preferred compounds of formula XXIX include those wherein R^(A3),R^(A4), R^(A5), R^(A6), and R^(A7) are independently C₁-C₆ alkyl orsiloxy. Preferably R^(A3), R^(A4), R^(A5), R^(A6), and R^(A7) areindependently selected from methyl, ethyl, n-propyl, n-butyl, andtrimethylsiloxy. More preferably, R^(A3), R^(A4), R^(A5), R^(A6), andR^(A7) are independently selected from methyl, n-butyl, andtrimethylsiloxy.

Preferred compounds of formula XXIX include those wherein R^(A3) andR^(A4) are independently C₁-C₆ alkyl (e.g., methyl or ethyl) or siloxy(e.g., trimethylsiloxy), and R^(A5), R^(A6), and R^(A)3 areindependently C₁-C₆ alkyl (e.g., methyl, ethyl, n-propyl, or n-butyl).

The silicone component may, for instance, have a number averagemolecular weight of from about 400 to about 4000 Daltons.

Examples of silicone-containing components suitable for use in theinvention include, but are not limited to, compounds listed in Table A.Where the compounds in Table B contain polysiloxane groups, the numberof SiO repeat units in such compounds, unless otherwise indicated, ispreferably from 3 to 100, more preferably from 3 to 40, or still morepreferably from 3 to 20.

TABLE A 1 mono-methacryloxypropyl terminated mono-n-butyl terminatedpolydimethylsiloxanes (mPDMS) (preferably containing from 3 to 15 SiOrepeating units) 2 mono-acryloxypropyl terminated mono-n-butylterminated polydimethylsiloxane 3 mono(meth)acryloxypropyl terminatedmono-n-methyl terminated polydimethylsiloxane 4 mono(meth)acryloxypropylterminated mono-n-butyl terminated polydiethylsiloxane 5mono(meth)acryloxypropyl terminated mono-n-methyl terminatedpolydiethylsiloxane 6 mono(meth)acrylamidoalkylpolydialkylsiloxanes 7mono(meth)acryloxyalkyl terminated mono-alkyl polydiarylsiloxanes 83-methacryloxypropyltris(trimethylsiloxy)silane (TRIS) 93-methacryloxypropylbis(trimethylsiloxy)methylsilane 103-methacryloxypropylpentamethyl disiloxane 11mono(meth)acrylamidoalkylpolydialkylsiloxanes 12mono(meth)acrylamidoalkyl polydimethylsiloxanes 13N-(2,3-dihydroxypropane)-N′-(propyl tetra(dimethylsiloxy)dimethylbutylsilane)acrylamide 14N-[3-tris(trimethylsiloxy)silyl]-propyl acrylamide (TRIS-Am) 152-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propylmethacrylate (SiMAA) 162-hydroxy-3-methacryloxypropyloxypropyl-tris(trimethylsiloxy)silane 17mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminatedmono-n-butyl terminated polydimethylsiloxanes (OH-mPDMS) (containingfrom 4 to 30, or from 10 to 20, or from 4 to 8 SiO repeat units) 18

19

20

21

22

23

24

Additional non-limiting examples of suitable silicone-containingcomponents are listed in Table B. Unless otherwise indicated, j2 whereapplicable is preferably from 1 to 100, more preferably from 3 to 40, orstill more preferably from 3 to 15. In compounds containing j1 and j2,the sum of j1 and j2 is preferably from 2 to 100, more preferably from 3to 40, or still more preferably from 3 to 15.

TABLE B 25

26

27

28

29

30 1,3-bis[4-(vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane 313-(vinyloxycarbonylthio) propyl-[tris (trimethylsiloxy)silane] 323-[tris(trimethylsiloxy)silyl] propyl allyl carbamate 333-[tris(trimethylsiloxy)silyl] propyl vinyl carbamate 34tris(trimethylsiloxy)silylstyrene (Styryl-TRIS) 35

36

37

38

39

40

41

The ethylenically unsaturated compound for inclusion in the firstreactive composition and/or the second reactive composition may comprisean independently selected hydrophilic component. Hydrophilic componentsinclude those which are capable of providing at least about 2000 or atleast about 25% o water content to the resulting composition whencombined with the remaining reactive components. Suitable hydrophiliccomponents include hydrophilic monomers, prepolymers and polymers.Preferably, the hydrophilic component has at least one reactive groupand at least one hydrophilic functional group. Examples of reactivegroups include acrylic, methacrylic, acrylamido, methacrylamido,fumaric, maleic, styryl, isopropenylphenyl, O-vinylcarbonate,O-vinylcarbamate, allylic, O-vinylacetyl and N-vinyllactam andN-vinylamido double bonds.

The term “vinyl-type” or “vinyl-containing” monomers refer to monomerscontaining the vinyl grouping (—CH═CH₂) and are generally highlyreactive. Such hydrophilic vinyl-containing monomers are known topolymerize relatively easily.

“Acrylic-type” or “acrylic-containing” monomers are those monomerscontaining an acrylic group (CH₂═CRCOX) wherein R is H or CH₃, and X isO or N, which are also known to polymerize readily, such as N,N-dimethylacrylamide (DMA), 2-hydroxyethyl methacrylamide, polyethyleneglycolmonomethacrylate, methacrylic acid, acrylic acid, mixtures thereof andthe like.

Hydrophilic monomers with at least one hydroxyl group (hydroxyalkylmonomer) may be used. The hydroxyl alkyl group may be selected fromC₂-C₄ mono or dihydroxy substituted alkyl, and poly(ethylene glycol)having 1-10 repeating units; or is selected from 2-hydroxyethyl,2,3-dihydroxypropyl, or 2-hydroxypropyl, and combinations thereof.

Examples of hydroxyalkyl monomers include 2-hydroxyethyl (meth)acrylate(HEMA), 3-hydroxypropyl (meth)acrylate, 2-hydroxypropyl (meth)acrylate,2,3-dihydroxypropyl (meth)acrylate, 2-hydroxybutyl (meth)acrylate,3-hydroxybutyl (meth)acrylate, 1-hydroxypropyl 2-(meth)acrylate,2-hydroxy-2-methyl-propyl (meth)acrylate, 3-hydroxy-2,2-dimethyl-propyl(meth)acrylate, 4-hydroxybutyl (meth)acrylate, 2-hydroxyethyl(meth)acrylamide, N-(2-hydroxypropyl) (meth)acrylamide,N,N-bis(2-hydroxyethyl) (meth)acrylamide, N,N-bis(2-hydroxypropyl)(meth)acrylamide, N-(3-hydroxypropyl) (meth)acrylamide,2,3-dihydroxypropyl (meth)acrylamide, glycerol (meth)acrylate,polyethyleneglycol monomethacrylate, and mixtures thereof.

The hydroxyalkyl monomer may also be selected from the group consistingof 2-hydroxyethyl methacrylate, glycerol methacrylate, 2-hydroxypropylmethacrylate, hydroxybutyl methacrylate, 3-hydroxy-2,2-dimethyl-propylmethacrylate, and mixtures thereof.

The hydroxyalkyl monomer may comprise 2-hydroxyethyl methacrylate,3-hydroxy-2,2-dimethyl-propyl methacrylate, hydroxybutyl methacrylate orglycerol methacrylate.

When hydrophilic polymers in quantities great than about 3 wt % aredesired, Hydroxyl containing (meth)acrylamides are generally toohydrophilic to be included as compatibilizing hydroxyalkyl monomers, andhydroxyl containing (meth)acrylates may be included in the reactivecomposition and the lower amount of hydroxyalkyl monomers may beselected to provide a haze value to the final lens of less than about50% or less than about 30%.

It will be appreciated that the amount of hydroxyl component will varydepending upon a number of factors, including, the number of hydroxylgroups on the hydroxyalkyl monomer, the amount, molecular weight andpresence of hydrophilic functionality on the silicone containingcomponents. The hydrophilic hydroxyl component may be present in thereactive composition in amounts up to about 15%, up to about 10 wt %,between about 3 and about 15 wt % or about 5 and about 15 wt %.

Hydrophilic vinyl-containing monomers which may be incorporated into thepolymer compositions include monomers such as hydrophilic N-vinyl lactamand N-vinyl amide monomers including: N-vinyl pyrrolidone (NVP),N-vinyl-2-piperidone, N-vinyl-2-caprolactam,N-vinyl-3-methyl-2-caprolactam, N-vinyl-3-methyl-2-piperidone,N-vinyl-4-methyl-2-piperidone, N-vinyl-4-methyl-2-caprolactam,N-vinyl-3-ethyl-2-pyrrolidone, N-vinyl-4,5-dimethyl-2-pyrrolidone,N-vinyl acetamide (NVA), N-vinyl-N-methylacetamide (VMA),N-vinyl-N-ethyl acetamide, N-vinyl-N-ethyl formamide, N-vinyl formamide,N-vinyl-N-methylpropionamide, N-vinyl-N-methyl-2-methylpropionamide,N-vinyl-2-methylpropionamide, N-vinyl-N,N′-dimethylurea,1-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone; 1-ethyl-5-methylene-2-pyrrolidone,N-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,1-N-propyl-3-methylene-2-pyrrolidone,1-N-propyl-5-methylene-2-pyrrolidone,1-isopropyl-3-methylene-2-pyrrolidone,1-isopropyl-5-methylene-2-pyrrolidone, N-vinyl-N-ethyl acetamide,N-vinyl-N-ethyl formamide, N-vinyl formamide, N-vinyl isopropylamide,N-vinyl caprolactam, N-carboxyvinyl-β-alanine (VINAL),N-carboxyvinyl-α-alanine, N-vinylimidazole, and mixtures thereof.

Hydrophilic O-vinyl carbamates and O-vinyl carbonates monomersincluding: N-2-hydroxyethyl vinyl carbamate and N-carboxy-β-alanineN-vinyl ester. Further examples of the hydrophilic vinyl carbonate orvinyl carbamate monomers are disclosed in U.S. Pat. No. 5,070,215, andthe hydrophilic oxazolone monomers are disclosed in U.S. Pat. No.4,910,277.

Vinyl carbamates and carbonates, including N-2-hydroxyethyl vinylcarbamate, N-carboxy-β-alanine N-vinyl ester, other hydrophilic vinylmonomers, including vinylimidazole, ethylene glycol vinyl ether (EGVE),di(ethylene glycol) vinyl ether (DEGVE), allyl alcohol, 2-ethyloxazoline, vinyl acetate, acrylonitrile, and mixtures thereof.

(Meth)acrylamide monomers may also be included as hydrophilic monomers.Examples include N—N-dimethylacrylamide, acrylamide,N,N-bis(2-hydroxyethyl)acrylamide, acrylonitrile, N-isopropylacrylamide, N,N-dimethylaminopropyl(meth)acrylamide, and any of thehydroxyl functional (meth)acrylamides listed above.

The hydrophilic monomers which may be incorporated into the polymersdisclosed herein may be selected from N,N-dimethyl acrylamide (DMA),2-hydroxyethyl acrylamide, 2-hydroxyethyl methacrylamide,N-hydroxypropyl methacrylamide, bishydroxyethyl acrylamide,2,3-dihydroxypropyl (meth)acrylamide, N-vinylpyrrolidone (NVP),N-vinyl-N-methyl acetamide, N-vinyl methacetamide (VMA), andpolyethyleneglycol monomethacrylate.

The hydrophilic monomers may be selected from DMA, NVP, VMA, NVA, andmixtures thereof.

The hydrophilic monomers may be macromers of linear or branchedpoly(ethylene glycol), poly(propylene glycol), or statistically randomor block copolymers of ethylene oxide and propylene oxide. The macromerof these polyethers has one reactive group. Non-limiting examples ofsuch reactive groups are acrylates, methacrylates, styrenes, vinylethers, acrylamides, methacrylamides, and other vinyl compounds. Themacromer of these polyethers may comprise acrylates, methacrylates,acrylamides, methacrylamides, and mixtures thereof. Other suitablehydrophilic monomers will be apparent to one skilled in the art.

The hydrophilic monomers may also comprise charged monomers includingbut not limited to acrylic acid, methacrylic acid, 3-acrylamidopropionicacid (ACA1), 4-acrylamidobutanoic acid, 5-acrylamidopentanoic acid(ACA2), 3-acrylamido-3-methylbutanoic acid (AMBA),N-vinyloxycarbonyl-α-alanine, N-vinyloxycarbonyl-β-alanine (VINAL),2-vinyl-4,4-dimethyl-2-oxazolin-5-one (VDMO), reactive sulfonate salts,including, sodium-2-(acrylamido)-2-methylpropane sulphonate (AMPS),3-sulphopropyl (meth)acrylate potassium salt, 3-sulphopropyl(meth)acrylate sodium salt, bis 3-sulphopropyl itaconate di sodium, bis3-sulphopropyl itaconate di potassium, vinyl sulphonate sodium salt,vinyl sulphonate salt, styrene sulfonate, sulfoethyl methacrylate,combinations thereof and the like.

The hydrophilic monomers may be selected from N, N-dimethyl acrylamide(DMA), N-vinylpyrrolidone (NVP), 2-hydroxyethyl methacrylate (HEMA),N-vinyl methacetamide (VMA), and N-vinyl N-methyl acetamide (NVA),N-hydroxypropyl methacrylamide, mono-glycerol methacrylate,2-hydroxyethyl acrylamide, 2-hydroxyethyl methacrylamide,bishydroxyethyl acrylamide, 2,3-dihydroxypropyl (meth)acrylamide andmixtures thereof.

The hydrophilic monomers may be selected from DMA, NVP, HEMA, VMA, NVA,and mixtures thereof.

The hydrophilic monomer(s) (including the hydroxyl alkyl monomers) maybe present in amounts up to about 60 wt %, between about 1 to about 60weight %, between about 5 to about 50 weight %, or about 5 to about 40weight %, based upon the weight of all reactive components.

Other hydrophilic monomers that can be employed include polyoxyethylenepolyols having one or more of the terminal hydroxyl groups replaced witha reactive group. Examples include polyethylene glycol with one or moreof the terminal hydroxyl groups replaced with a reactive group. Examplesinclude polyethylene glycol reacted with one or more molar equivalentsof an end-capping group such as isocyanatoethyl methacrylate (“IEM”),methacrylic anhydride, methacryloyl chloride, vinylbenzoyl chloride, orthe like, to produce a polyethylene polyol having one or more terminalpolymerizable olefinic groups bonded to the polyethylene polyol throughlinking moieties such as carbamate or ester groups.

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,190,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Hydrophilic monomers which may be incorporated into the polymercompositions disclosed herein include hydrophilic monomers such asN,N-dimethyl acrylamide (DMA), 2-hydroxyethyl acrylate, glycerolmethacrylate, 2-hydroxyethyl methacrylamide, N-vinylpyrrolidone (NVP),N-vinyl methacrylamide, HEMA, and poly(ethyleneglycol) methyl ethermethacrylate (mPEG).

Hydrophilic monomers may include DMA, NVP, HEMA and mixtures thereof.

The first reactive composition and/or the second reactive compositionmay contain one or more independently selected ethylenically unsaturatedzwitterionic compounds, such as an ethylenically unsaturated betaine.Preferably, the zwitterionic compound is in the second reactivecomposition. Examples of suitable compounds include:N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-1-propanaminium,inner salt (CAS 79704-35-1, also known as3-acrylamido-N-(2-carboxyethyl)-N,N-dimethylpropane-1-aminium or CBT);3-methacrylamido-N-(2-carboxyethyl)-N,N-dimethylpropane-1-aminium;N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-1-propanaminium,inner salt (CAS 80293-60-3, also known as 3-((3-acrylamidopropyl)dimethylammonio) propane-1-sulfonate or SBT);3-((3-methacrylamidopropyl) dimethylammonio) propane-1-sulfonate;3,5-Dioxa-8-aza-4-phosphaundec-10-en-1-aminium,4-hydroxy-N,N,N-trimethyl-9-oxo, inner salt, 4-oxide (CAS 163674-35-9,“PBT”); 2-(acrylamidoethoxy)-(2-(trimethylammonio)ethyl) phosphate;2-(methacrylamidoethoxy)-(2-(trimethylammonio)ethyl) phosphate;4-hydroxy-N,N,N,10-tetramethyl-9-oxo-3,5,8-trioxa-4-phosphaundec-10-en-1-aminiuminner salt, 4-oxide (CAS 67881-98-5, also known as2-(methacryloyloxy)ethyl (2-(trimethylammonio)ethyl) phosphate or MPC);or 2-(acryloyloxy)ethyl (2-(trimethylammonio)ethyl) phosphate.

The first reactive composition and/or the second reactive compositionmay contain one or more independently selected ethylenically unsaturatedquaternary ammonium salts. Preferably, the quaternary ammonium salt isin the second reactive composition. Examples of suitable compoundsinclude 2-(methacryloyloxy)ethyl trimethylammonium chloride;2-(acryloyloxy)ethyl trimethylammonium chloride;3-methacrylamido-N,N,N-trimethylpropan-1-aminium chloride; or3-acrylamido-N,N,N-trimethylpropan-1-aminium chloride

The first reactive composition and/or the second reactive compositionmay contain one or more independently selected ethylenically unsaturatedactive pharmaceutical ingredients. Preferably, the active pharmaceuticalcompound is in the second reactive composition. Examples of suitablecompounds include cyclosporine or salicylate monomers.

The first reactive composition and/or the second reactive compositionmay contain one or more independently selected ethylenically unsaturatedpeptides. Preferably, the peptide is in the second reactive composition.Exemplary compounds include, for instance, those wherein theamino-terminus of a peptide may be acylated with an acylating agent suchas (meth)acryloyl chloride, (meth)acrylic anhydride, isopropenylα,α-dimethylbenzyl isocyanate and 2-isocyanatoethyl methacrylate alongwith known co-reagents and catalysts to form a monomer suitable forincorporation into reactive compositions of the present inventions

The first reactive composition of the invention contains a crosslinker.Crosslinkers may optionally be present in the second reactivecomposition. A variety of crosslinkers may be used, includingsilicone-containing and non-silicone containing cross-linking agents,and mixtures thereof. Examples of suitable crosslinkers include ethyleneglycol dimethacrylate (EGDMA), diethyleneglycol dimethacrylate,trimethylolpropane trimethacrylate (TMPTMA), tetraethylene glycoldimethacrylate (TEGDMA), triallyl cyanurate (TAC), glyceroltrimethacrylate, 1,3-propanediol dimethacrylate; 2,3-propanedioldimethacrylate; 1,6-hexanediol dimethacrylate; 1,4-butanedioldimethacrylate, methacryloxyethyl vinylcarbonate (HEMAVc),allylmethacrylate, methylene bisacrylamide (MBA), polyethylene glycoldimethacrylate (wherein the polyethylene glycol preferably has amolecular weight up to 5,000 Daltons). The crosslinkers are used in thetypical amounts known to those skilled in the art, e.g., from about0.000415 to about 0.0156 mole per 100 grams of reactive components inthe reaction composition.

It should be noted that if the ethylenically unsaturated compound, suchas a hydrophilic monomer or a silicone containing monomer, acts as thecrosslinker, for instance by virtue of being bifunctional ormultifunctional, the addition of a separate crosslinker to the reactioncomposition is optional. In this case, the ethylenically unsaturatedcompound is also considered a crosslinker. Examples of hydrophilicmonomers which can act as the crosslinking agent and when present do notrequire the addition of an additional crosslinking agent to the reactioncomposition include polyoxyethylene polyols described above containingtwo or more terminal methacrylate moieties. An example of a siliconecontaining monomer which can act as a crosslinking agent and, whenpresent, does not require the addition of a crosslinking monomer to thereaction composition includes α,ω-bismethacryloypropylpolydimethylsiloxane. In addition, any of the above disclosedmultifunctional silicone-containing components may be used ascross-linking agents.

Either or both of the first and second reactive compositions may containadditional components such as, but not limited to, UV absorbers,photochromic compounds, pharmaceutical and nutraceutical compounds,antimicrobial compounds, reactive tints, pigments, copolymerizable andnon-polymerizable dyes, release agents and combinations thereof. Othercomponents that can be present in the first and/or second reactivecompositions include wetting agents, such as those disclosed in U.S.Pat. No. 6,367,929, WO03/22321, WO03/22322, compatibilizing components,such as those disclosed in US2003/162862 and US2003/125498. The sum ofadditional components may be up to about 20 wt %. The reactivecompositions may comprise up to about 18 wt % wetting agent, or betweenabout 5 and about 18 wt % wetting agent.

As used herein, wetting agents are hydrophilic polymers having a weightaverage molecular weight greater than about 5,000 Daltons, between about150,000 Daltons to about 2,000,000 Daltons; between about 300,000Daltons to about 1,800,000 Daltons; or between about 500,000 Daltons toabout 1,500,000 Daltons.

The amount of optional wetting agent which may be added to the reactivecompositions of the present invention may be varied depending on theother components used and the desired properties of the resultingproduct. When present, the internal wetting agents in reactivecompositions may be included in amounts from about 1 weight percent toabout 20 weight percent; from about 2 weight percent to about 15percent, or from about 2 to about 12 percent, all based upon the totalweight of all of the reactive components.

Wetting agents include but are not limited to homopolymers,statistically random copolymers, diblock copolymers, triblockcopolymers, segmented block copolymers, graft copolymers, and mixturesthereof. Non-limiting examples of internal wetting agents arepolyamides, polyesters, polylactones, polyimides, polylactams,polyethers, polyacids homopolymers and copolymers prepared by the freeradical polymerization of suitable monomers including acrylates,methacrylates, styrenes, vinyl ethers, acrylamides, methacrylamides,N-vinyllactams, N-vinylamides, O-vinylcarbamates, 0-vinylcarbonates, andother vinyl compounds. The wetting agents may be made from anyhydrophilic monomer, including those listed herein.

The wetting agents may include acyclic polyamides comprise pendantacyclic amide groups and are capable of association with hydroxylgroups. Cyclic polyamides comprise cyclic amide groups and are capableof association with hydroxyl groups.

Examples of suitable acyclic polyamides include polymers and copolymerscomprising repeating units of Formula XXIX or Formula XXX:

-   -   wherein X is a direct bond, —(CO)—, or —(CO)—NHR^(e)—, wherein        R²⁶ and R¹⁷ are H or methyl groups; wherein R^(e) is a C₁ to C₃        alkyl group; R^(a) is selected from H, straight or branched,        substituted or unsubstituted C₁ to C₄ alkyl groups; R^(b) is        selected from H, straight or branched, substituted or        unsubstituted C₁ to C₄ alkyl groups, amino groups having up to        two carbon atoms, amide groups having up to four carbon atoms,        and alkoxy groups having up to two carbon groups; R^(c) is        selected from H, straight or branched, substituted or        unsubstituted C₁ to C₄ alkyl groups, or methyl, ethoxy,        hydroxyethyl, and hydroxymethyl; R^(d) is selected from H,        straight or branched, substituted or unsubstituted C₁ to C₄        alkyl groups; or methyl, ethoxy, hydroxyethyl, and hydroxymethyl        wherein the number of carbon atoms in R^(a) and R^(b) taken        together is 8 or less, including 7, 6, 5, 4, 3, or less, and        wherein the number of carbon atoms in R^(c) and R^(d) taken        together is 8 or less, including 7, 6, 5, 4, 3, or less. The        number of carbon atoms in R^(a) and R^(b) taken together may be        6 or less or 4 or less. The number of carbon atoms in R^(c) and        R^(d) taken together may be 6 or less. As used herein        substituted alkyl groups include alkyl groups substituted with        an amine, amide, ether, hydroxyl, carbonyl, carboxy groups or        combinations thereof.

R^(a) and R^(b) can be independently selected from H, substituted orunsubstituted C₁ to C₂ alkyl groups. X may be a direct bond, and R^(a)and R^(b) may be independently selected from H, substituted orunsubstituted C₁ to C₂ alkyl groups.

R^(c) and R^(d) can be independently selected from H, substituted orunsubstituted C₁ to C₂ alkyl groups, methyl, ethoxy, hydroxyethyl, andhydroxymethyl.

The acyclic polyamides of the present invention may comprise a majorityof the repeating unit of Formula XXIX or Formula XXX, or the acyclicpolyamides can comprise at least about 50 mole % of the repeating unitof Formula XXIX or Formula XXX, including at least about 70 mole %, andat least 80 mole %.

Specific examples of repeating units of Formula XXIX or Formula XXXinclude repeating units derived from N-vinyl-N-methylacetamide,N-vinylacetamide, N-vinyl-%-methylpropionamide,N-vinyl-N-ethyl-2-methylpropionamide, N-vinyl-2-methylpropionamide,N-vinyl-N,N′-dimethylurea, V, N-dimethylacrylamide, methacrylamide andacyclic amides of Formulae XXXI and XXXII:

Examples of suitable cyclic amides that can be used to form the cyclicpolyamides of include α-lactam, β-lactam, γ-lactam, δ-lactam, andε-lactam. Examples of suitable cyclic polyamides include polymers andcopolymers comprising repeating units of Formula XXXIII:

-   -   wherein f is a number from 1 to 10, X is a direct bond, —(CO)—,        or —(CO)—NH—R^(e)—, wherein R^(e) is a C₁ to C₃ alkyl group and        R²⁸ is a hydrogen atom or methyl group. In Formula XXXIII, f may        be 8 or less, including 7, 6, 5, 4, 3, 2, or 1. In Formula        XXXIII, f may be 6 or less, including 5, 4, 3, 2, or 1, or may        be from 2 to 8, including 2, 3, 4, 5, 6, 7, or 8, or may be 2 or        3.

When X is a direct bond, f may be 2. In such instances, the cyclicpolyamide may be polyvinylpyrrolidone (PVP).

The cyclic polyamides may comprise 50 mole % or more of the repeatingunit of Formula XXXIII, or the cyclic polyamides can comprise at leastabout 50 mole % of the repeating unit of Formula XXXIII, including atleast about 70 mole %, and at least about 80 mole %.

Specific examples of repeating units of Formula XXXIII include repeatingunits derived from N-vinylpyrrolidone, which forms PVP homopolymers andvinylpyrrolidone copolymers or N-vinylpyrrolidone substituted withhydrophilic substituents such as phosphoryl choline.

The polyamides may also be copolymers comprising cyclic amide, acyclicamide repeating units or copolymers comprising both cyclic and acyclicamide repeating units. Additional repeating units may be formed frommonomers selected from hydroxyalkyl(meth)acrylates, alkyl(meth)acrylatesor other hydrophilic monomers and siloxane substituted acrylates ormethacrylates. Any of the monomers listed as suitable hydrophilicmonomers may be used as comonomers to form the additional repeatingunits. Specific examples of additional monomers which may be used toform polyamides include 2-hydroxyethylmethacrylate, vinyl acetate,acrylonitrile, hydroxypropyl methacrylate, 2-hydroxyethyl acrylate,methyl methacrylate and hydroxybutyl methacrylate, GMMA, PEGS, and thelike and mixtures thereof. Ionic monomers may also be included. Examplesof ionic monomers include acrylic acid, methacrylic acid,2-methacryloyloxyethyl phosphorylcholine,3-(dimethyl(4-vinylbenzyl)ammonio)propane-1-sulfonate (DMVBAPS),3-((3-acrylamidopropyl)dimethylammonio)propane-1-sulfonate (AMPDAPS),3-((3-methacrylamidopropyl)dimethylammonio)propane-1-sulfonate(MAMPDAPS),3-((3-(acryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (APDAPS),methacryloyloxy)propyl)dimethylammonio)propane-1-sulfonate (MAPDAPS).

The reactive composition may comprise both an acyclic polyamide and acyclic polyamide or copolymers thereof. The acyclic polyamide can be anyof those acyclic polyamides described herein or copolymers thereof, andthe cyclic polyamide can be any of those cyclic polyamides describedherein or copolymers thereof. The polyamide may be selected from thegroup polyvinylpyrrolidone (PVP), polyvinylmethyacetamide (PVMA),polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA),poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers andmixtures thereof.

The wetting agents may be made from DMA, NVP, HEMA, VMA, NVA, andcombinations thereof. The wetting agents may also be reactivecomponents, as defined herein, by having reactive groups, for example,made by the acylation reaction between pendant hydroxyl groups on HEMArepeating units of an internal wetting agent and methacryloyl chlorideor methacryloyl anhydride. Other methods of functionalization will beapparent to one skilled in the art.

Such internal wetting agents are disclosed in U.S. Pat. Nos. 6,367,929,6,822,016, 7,052,131, 7,666,921, 7,691,916, 7,786,185, 8,022,158, and8,450,387.

Generally, the reactive components within a reactive composition may bedispersed or dissolved in a diluent. Suitable diluents are known in theart or can be easily determined by a person of ordinary skill in theart. For example, when silicone hydrogels are being prepared, suitablediluents are disclosed in WO 03/022321 and U.S. Pat. No. 6,020,445 thedisclosures of which are incorporated herein by reference.

Classes of suitable diluents for silicone hydrogel reaction mixturesinclude alcohols having 2 to 20 carbons, amides having 10 to 20 carbonatoms derived from primary amines and carboxylic acids having 8 to 20carbon atoms. Primary and tertiary alcohols are preferred. Preferredclasses include alcohols having 5 to 20 carbons and carboxylic acidshaving 10 to 20 carbon atoms.

Specific diluents which may be used include 1-ethoxy-2-propanol,diisopropylaminoethanol, isopropanol, 3,7-dimethyl-3-octanol, 1-decanol,1-dodecanol, 1-octanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol,2-octanol, 3-methyl-3-pentanol, tert-amyl alcohol, tert-butanol,2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-propanol, 1-propanol,ethanol, 2-ethyl-1-butanol,(3-acetoxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy) methylsilane,1-tert-butoxy-2-propanol, 3,3-dimethyl-2-butanol, tert-butoxyethanol,2-octyl-1-dodecanol, decanoic acid, octanoic acid, dodecanoic acid,2-(diisopropylamino)ethanol mixtures thereof and the like.

Preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol,1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol,3-methyl-3-pentanol, 2-pentanol, t-amyl alcohol, tert-butanol,2-butanol, 1-butanol, 2-methyl-2-pentanol, 2-ethyl-1-butanol, ethanol,3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, decanoic acid, octanoicacid, dodecanoic acid, mixtures thereof and the like.

More preferred diluents include 3,7-dimethyl-3-octanol, 1-dodecanol,1-decanol, 1-octanol, 1-pentanol, 1-hexanol, 2-hexanol, 2-octanol,1-dodecanol, 3-methyl-3-pentanol, 1-pentanol, 2-pentanol, t-amylalcohol, tert-butanol, 2-butanol, 1-butanol, 2-methyl-2-pentanol,2-ethyl-1-butanol, 3,3-dimethyl-2-butanol, 2-octyl-1-dodecanol, mixturesthereof and the like.

Suitable diluents for non-silicone containing reaction compositionsinclude glycerin, ethylene glycol, ethanol, methanol, ethyl acetate,methylene chloride, polyethylene glycol, polypropylene glycol, lownumber average molecular weight polyvinylpyrrolidone (PVP), such asdisclosed in U.S. Pat. Nos. 4,018,853, 4,680,336 and 5,039,459,including, but not limited to boric acid esters of dihydric alcohols,combinations thereof and the like.

Mixtures of diluents may be used. The diluents may be used in amounts upto about 55% by weight of the total of all components in the reactivecomposition. More preferably the diluent is used in amounts less thanabout 45% and more preferably in amounts between about 15 and about 40%by weight of the total of all components in the reactive composition.

The polymer compositions described above may be used in a wide varietyof fields. A preferred use is in medical devices. Thus, in a preferredembodiment, the invention provides a medical device comprising a polymercomposition, wherein the polymer composition is prepared as describedabove. Preferred medical devices are ophthalmic devices, such as contactlenses, intraocular lenses, punctal plugs and ocular inserts.Particularly preferred are contact lenses.

In some embodiments, well suited for ophthalmic devices and contactlenses, the polymer composition is a hydrogel.

The polymer composition may be a hydrogel and the first reactivecomposition may contain one or more silicone containing components.Exemplary silicone containing components include the compounds disclosedabove, or mixtures thereof. Preferred silicone containing componentsinclude compounds of formula VIa (preferably Formula V), Formula XXc(preferably Formula XXg or SiMAA), or mixtures of thereof. The polymercomposition may also contain a hydrophilic component. Preferredhydrophilic components include acrylic containing hydrophiliccomponents, such as N,N-dimethylacrylamide (DMA), 2-hydroxyethyl(meth)acrylate, and mixtures thereof. The polymer composition maycontain a wetting agent. Preferred wetting agents include polyamides,such those selected from polyvinylpyrrolidone (PVP),polyvinylmethyacetamide (PVMA), polydimethylacrylamide (PDMA),polyvinylacetamide (PNVA), poly(hydroxyethyl(meth)acrylamide),polyacrylamide, and copolymers and mixtures thereof.

The polymer composition may be a hydrogel and the first reactivecomposition may contain one or more hydrophilic components. Exemplaryhydrophilic components include acrylic containing hydrophilic componentsand vinyl-containing monomers, such as N,N-dimethylacrylamide (DMA),2-hydroxyethyl (meth)acrylate, glycerol methacrylate, 2-hydroxyethylmethacrylamide, polyethyleneglycol monomethacrylate, methacrylic acid,acrylic acid, N-vinylpyrrolidone (NVP), N-vinyl methacrylamide, ormixtures thereof. Preferred hydrophilic compounds include 2-hydroxyethylmethacrylate, methacrylic acid, or mixtures thereof. The first reactivecomposition may be free of silicone containing components.

The polymer composition may be a hydrogel and the second reactivecomposition may contain one or more silicone containing components.Exemplary silicone containing components include the compounds disclosedabove, or mixtures thereof. Preferred silicone containing componentsinclude compounds of formula VIa (preferably mPDMS), Formula XXc(preferably SiMAA), or mixtures of thereof. The polymer composition mayalso contain a hydrophilic component. Preferred hydrophilic componentsinclude acrylic containing hydrophilic components, such asN,N-dimethylacrylamide (DMA), 2-hydroxyethyl (meth)acrylate, andmixtures thereof. The polymer composition may contain a wetting agent.Preferred wetting agents include polyamides, such those selected frompolyvinylpyrrolidone (PVP), polyvinylmethyacetamide (PVMA),polydimethylacrylamide (PDMA), polyvinylacetamide (PNVA),poly(hydroxyethyl(meth)acrylamide), polyacrylamide, and copolymers andmixtures thereof.

The polymer composition may be a hydrogel and the second reactivecomposition may contain one or more hydrophilic components. Exemplaryhydrophilic components include acrylic containing hydrophilic componentsand vinyl-containing monomers, such as N,N-dimethylacrylamide (DMA),2-hydroxyethyl (meth)acrylate, glycerol methacrylate, 2-hydroxyethylmethacrylamide, polyethyleneglycol monomethacrylate, methacrylic acid,acrylic acid, N-vinylpyrrolidone (NVP), N-vinyl methacrylamide, ormixtures thereof. Preferred hydrophilic compounds include 2-hydroxyethylmethacrylate, methacrylic acid, or mixtures thereof. The second reactivecomposition may be free of silicone containing components.

The polymer composition may be a hydrogel and the ethylenicallyunsaturated compounds of the first reactive composition and the secondreactive composition may be independently selected from: a(meth)acrylate monomer, a (meth)acrylic acid monomer, a siliconecontaining component, and mixtures of two or more thereof. Preferredreactive components for the second reactive composition of thisembodiment may include MPC, 2-hydroxyethyl methacrylate, or a mixture of2-hydroxyethyl methacrylate and methacrylic acid.

The polymer composition may be a hydrogel and the ethylenicallyunsaturated compounds of the first reactive composition and the secondreactive composition may be independently selected from: a siliconecontaining component, a (meth)acrylate monomer, a (meth)acrylic acidmonomer, an ethylenically unsaturated betaine, a (meth)acrylamide, anethylenically unsaturated polyethylene glycol, an N-vinyl monomer, anethylenically unsaturated amino acid, and mixtures of two or morethereof.

The crosslinked substrate network may be a silicone hydrogel (containingMAPO groups) and the second reactive composition may provide, followingpolymerization, a hydrophilic grafted material (which may optionally becharged), for instance comprising poly(N,N-dimethylacrylamide) (PDMA),polymerized polyethylene glycol mono-methacrylate, (poly(mPEG)), or acopolymer of 2-hydroxyethyl methacrylate and methacrylic acid. Suchgrafted polymer networks may exhibit improved biocompatibility andbiometrics, for instance when used in ophthalmic devices.

The crosslinked substrate network may be a conventional hydrogel (e.g.,comprising a copolymer of 2-hydroxyethyl methacrylate and methacrylicacid and containing MAPO groups) and the second reactive compositionprovides, following polymerization, a hydrophilic grafted material(which may optionally be charged), such as a polyamide. Examples includePDMA, polyvinylpyrrolidone (PVP), poly(N-vinyl N-methyl acetamide)(PVMA), and copolymers thereof. Such grafted polymer networks mayexhibit improved biocompatibility and biometrics, for instance when usedin ophthalmic devices.

The crosslinked substrate network may be a conventional hydrogel (e.g.,a copolymer of 2-hydroxyethyl methacrylate and methacrylic acid andcontaining MAPO groups) and the second reactive composition provides,following polymerization, a hydrophobic siloxane containing material.Such grafted polymeric networks may exhibit desirable physical andmechanical properties, such as oxygen gas permeability (Dk) and modulus,as well as improved biocompatibility and handling.

For ophthalmic devices, such as contact lenses, that contain one or moresilicone containing component, the silicone-containing component(s) maypreferably be present in amounts up to about 95 weight %, or from about10 to about 80, or from about 20 to about 70 weight %, based upon allreactive components present, including in the first reactive compositionand the reactive second composition. Suitable hydrophilic components maypreferably be present in amounts from about 10 to about 60 weight %, orfrom about 15 to about 50 weight %, or from about 20 to about 40 weight%, based upon all reactive components present, including in the firstreactive composition and the second reactive composition.

It should be noted that additional, optional, steps may be included inthe process for making the polymer compositions of the invention. Forinstance, following step (b), an ink or dye may be added to thecrosslinked substrate network. Then, the remaining steps (step (c) etc.)may be carried out. This allows for an ink or dye to be sandwichedwithin the grafted polymeric network.

For ophthalmic devices, such as contact lenses, the crosslinkedsubstrate network is preferably a silicone hydrogel with a balance ofproperties that makes them useful. These properties include watercontent, haze, contact angle, modulus, oxygen permeability, lipiduptake, lysozyme uptake and PQ1 uptake. Examples of preferred propertiesare as follows. All values are prefaced by “about,” and the ophthalmicdevices may have any combination of the listed properties:

-   -   [H₂O] %: at least 20%, or at least 25%    -   Haze: 30% or less, or 10% or less    -   DCA (°): 1000 or less, or 500 or less    -   Modulus (psi): 120 or less, or 80 to 120    -   Dk (barrers): at least 80, or at least 100, or at least 150, or        at least 200    -   Elongation to Break: at least 100        For ionic silicon hydrogels, the following properties may also        be preferred (in addition to those recited above):    -   Lysozyme uptake (μg/lens): at least 100, or at least 150, or at        least 500, or at least 700    -   PQ1 uptake (%): 15 or less, or 10 or less, or 5 or less

Finished ophthalmic devices may be manufactured by various techniques.For instance, in the case of hydrogel contact lenses, the first reactivecomposition described above may be cured in a mold, or formed viaspincasting or static casting. Spincasting methods are disclosed in U.S.Pat. Nos. 3,408,429 and 3,660,545, and static casting methods aredisclosed in U.S. Pat. Nos. 4,113,224 and 4,197,266. In one embodiment,the contact lenses of this invention are formed by the direct molding ofthe hydrogels, which is economical, and enables precise control over thefinal shape of the hydrated contact lens. For this method, the firstreactive composition is placed in a mold having the desired shape andthe reactive composition is subjected to conditions as described abovewhereby the reactive components polymerize to produce the crosslinkedsubstrate network in the approximate shape of the final desired product.

The crosslinked substrate network formed after such curing may besubjected to extraction to remove unreacted components and release thecrosslinked substrate network from the contact lens mold. Thecrosslinked substrate network may then be immersed in the secondreactive composition (which may optionally contain a diluent), andsufficient time is allowed to permit at least a portion of the reactivecomposition to diffuse into the crosslinked substrate network.Thereafter, the suspension is irradiated to form the grafted polymericnetwork, and the contact lenses may then be extracted to removeunreacted components.

Extractions of the crosslinked substrate network and the contact lensmay be done using conventional extraction fluids, such organic solvents,such as alcohols or may be extracted using aqueous solutions. Aqueoussolutions are solutions which comprise water. The aqueous solutions maycomprise at least about 30 weight % water, or at least about 50 weight %water, or at least about 70% water or at least about 90 weight % water.

Extraction may be accomplished, for example, via immersion of thecrosslinked substrate network or the contact lens in an aqueous solutionor exposing the material to a flow of an aqueous solution. Extractionmay also include, for example, one or more of: heating the aqueoussolution; stirring the aqueous solution; increasing the level of releaseaid in the aqueous solution to a level sufficient to cause release ofthe crosslinked substrate network from the mold; mechanical orultrasonic agitation; and incorporating at least one leach aid in theaqueous solution to a level sufficient to facilitate adequate removal ofunreacted components from the crosslinked substrate network or thecontact lens. The foregoing may be conducted in batch or continuousprocesses, with or without the addition of heat, agitation or both.

Some embodiments may also include the application of physical agitationto facilitate leach and release. For example, the crosslinked substratenetwork mold part to which the crosslinked substrate network is adheredmay be vibrated or caused to move back and forth within an aqueoussolution. Other embodiments may include ultrasonic waves through theaqueous solution.

Contact lenses may be sterilized by known means such as, but not limitedto, autoclaving.

Some embodiments of the invention will now be described in detail in thefollowing Examples.

EXAMPLES

The contact lens diameter (DM) was measured on a calibrated Van Keurenmicro optical comparator equipment equipped with Mitutoyo digimaticmicrometer heads. The contact lens was placed concave side down into acrystal cell completely filled with borate buffered packing solution. Acap was placed onto the cell ensuring that no air is trapped underneath.The cell was then placed on the comparator stage and the lens imagebrought into focus and aligned so that one edge of the lens touched thecenter line on the screen. The first edge was marked, the lens movedalong its diameter until the second edge is touching the center line onthe screen, and then, the second edge is marked by pushing the databutton again. Typically, two diameter measurements are made and theaverage reported in the data tables.

Water content (WC) was measured gravimetrically. Lenses wereequilibrated in packing solution for 24 hours. Each of three test lensare removed from packing solution using a sponge tipped swab and placedon blotting wipes which have been dampened with packing solution. Bothsides of the lens are contacted with the wipe. Using tweezers, the testlens are placed in a tared weighing pan and weighed. The two more setsof samples are prepared and weighed. All weight measurements were donein triplicate, and the average of those values used in the calculations.The wet weight is defined as the combined weight of the pan and wetlenses minus the weight of the weighing pan alone.

The dry weight was measured by placing the sample pans in a vacuum ovenwhich has been preheated to 60° C. for 30 minutes. Vacuum was applieduntil the pressure reaches at least 1 inch of Hg is attained; lowerpressures are allowed. The vacuum valve and pump are turned off and thelenses are dried for at least 12 hours, typically overnight. The purgevalve is opened allowing dry air or dry nitrogen gas to enter. The ovenis allowed reach atmospheric pressure. The pans are removed and weighed.The dry weight is defined as the combined weight of the pan and drylenses minus the weight of the weighing pan alone. The water content ofthe test lens was calculated as follows: % water content=(wet weight−dryweight)/wet weight×100. The average and standard deviation of the watercontent were calculated and the average value reported as the percentwater content of the test lens.

The grafted lens weight gain was calculated from the average dry weightof the grafted lens minus the average dry weight of the substrate lensand expressed as a percentage. Both the grafted lens and the substratelens were equilibrated in deionized water for several hours to removeany residual salts. Typically, at least three lenses are weighed andaveraged for each sample.

The refractive index (RI) of a contact lens was measured by a LeicaARIAS 500 Abbe refractometer in manual mode or by a Reichert ARIAS 500Abbe refractometer in automatic mode with a prism gap distance of 100microns. The instrument was calibrated using deionized water at 20° C.(+/−0.2° C.). The prism assembly was opened and the test lens placed onthe lower prism between the magnetic dots closest to the light source.If the prism is dry, a few drops of saline were applied to the bottomprism. The front curve of the lens was against the bottom prism. Theprism assembly was then closed. After adjusting the controls so that theshadow line appeared in the reticle field, the refractive index wasmeasured. The RI measurement was made on five test lenses. The averageRI calculated from the five measurements was recorded as the refractiveindex as well as its standard deviation.

Oxygen permeability (Dk) was determined by the polarographic methodgenerally described in ISO 9913-1:1996 and ISO 18369-4:2006, but withthe following modifications. The measurement was conducted at anenvironment containing 2.1% oxygen created by equipping the test chamberwith nitrogen and air inputs set at the appropriate ratio, for example,1800 mL/min of nitrogen and 200 mL/min of air. The t/Dk is calculatedusing the adjusted oxygen concentration. Borate buffered saline wasused. The dark current was measured by using a pure humidified nitrogenenvironment instead of applying MMA lenses. The lenses were not blottedbefore measuring. Four lenses were stacked instead of using lenses ofvarious thickness (t) measured in centimeters. A curved sensor was usedin place of a flat sensor; radius was 7.8 mm. The calculations for a 7.8mm radius sensor and 10% (v/v) air flow are as follows:

Dk/t=(measured current−dark current)×(2.97×10−8 mL O2/(μA-sec-cm2-mm Hg)

The edge correction was related to the Dk of the material.

For all Dk values less than 90 barrers:

t/Dk (edge corrected)=[1+(5.88×t)]×(t/Dk)

For Dk values between 90 and 300 barrers:

t/Dk (edge corrected)=[1+(3.56×t)]×(t/Dk)

For Dk values greater than 300 barrers:

t/Dk (edge corrected)=[1+(3.16×t)]×(t/Dk)

Non-edge corrected Dk was calculated from the reciprocal of the slopeobtained from the linear regression analysis of the data wherein the xvariable was the center thickness in centimeters and the y variable wasthe t/Dk value. On the other hand, edge corrected Dk (EC Dk) wascalculated from the reciprocal of the slope obtained from the linearregression analysis of the data wherein the x variable was the centerthickness in centimeters and the y variable was the edge corrected t/Dkvalue. The resulting Dk value was reported in barrers.

Wettability of lenses was determined by a modified Wilhelmy plate methodusing a calibrated Kruss K100 tensiometer at room temperature (23±4° C.)and using surfactant free borate buffered saline as the probe solution.All equipment must be clean and dry; vibrations must be minimal aroundthe instrument during testing. Wettability is usually reported as theadvancing contact angle (Kruss DCA). The tensiometer was equipped with ahumidity generator, and a temperature and humidity gage was placed inthe tensiometer chamber. The relative humidity was maintained at 70±5%.The experiment was performed by dipping the lens specimen of knownperimeter into the packing solution of known surface tension whilemeasuring the force exerted on the sample due to wetting by a sensitivebalance. The advancing contact angle of the packing solution on the lensis determined from the force data collected during sample dipping. Thereceding contact angle is determined from force data while withdrawingthe sample from the liquid. The Wilhelmy plate method is based on thefollowing formula: Fg=γρ cos θ−B, wherein F=the wetting force betweenthe liquid and the lens (mg), g=gravitational acceleration (980.665cm/sec²), γ=surface tension of probe liquid (dyne/cm), β=the perimeterof the contact lens at the liquid/lens meniscus (cm), θ=the dynamiccontact angle (degree), and B=buoyancy (mg). B is zero at the zero depthof immersion. Typically, a test strip was cut from the central area ofthe contact lens. Each strip was approximately 5 mm in width and 14 mmin length, attached to a metallic clip using plastic tweezers, piercedwith a metallic wire hook, and equilibrated in packing solution for atleast 3 hours. Then, each sample was cycled four times, and the resultswere averaged to obtain the advancing and receding contact angles of thelens. Typical measuring speeds were 12 mm/min. Samples were keptcompletely immersed in packing solution during the data acquisition andanalysis without touching the metal clip. Values from five individuallenses were averaged to obtain the reported advancing and recedingcontact angles of the experimental lens.

Wettability of lenses was determined using a sessile drop techniqueusing KRUSS DSA-100™ instrument at room temperature and using deionizedwater as probe solution (Sessile Drop). The lenses to be tested wererinsed in deionized water to remove carry over from packing solution.Each test lens was placed on blotting lint free wipes which weredampened with packing solution. Both sides of the lens were contactedwith the wipe to remove surface water without drying the lens. To ensureproper flattening, lenses were placed “bowl side down” on the convexsurface of contact lens plastic molds. The plastic mold and the lenswere placed in the sessile drop instrument holder, ensuring propercentral syringe alignment. A 3 to 4 microliter drop of deionized waterwas formed on the syringe tip using DSA 100-Drop Shape Analysis softwareensuring the liquid drop was hanging away from the lens. The drop wasreleased smoothly on the lens surface by moving the needle down. Theneedle was withdrawn away immediately after dispensing the drop. Theliquid drop was allowed to equilibrate on the lens for 5 to 10 seconds,and the contact angle was measured between the drop image and the lenssurface. Typically, three to five lenses were evaluated and the averagecontact angle reported.

The mechanical properties of the contact lenses were measured by using atensile testing machine such as an Instron model 1122 or 5542 equippedwith a load cell and pneumatic grip controls. Minus one diopter lens isthe preferred lens geometry because of its central uniform thicknessprofile. A dog-bone shaped sample cut from a −1.00 power lens having a0.522 inch length, 0.276 inch “ear” width and 0.213 inch “neck” widthwas loaded into the grips and elongated at a constant rate of strain of2 inches per minute until it breaks. The center thickness of thedog-bone sample was measured using an electronic thickness gauge priorto testing. The initial gauge length of the sample (Lo) and samplelength at break (Lf) were measured. At least five specimens of eachcomposition were measured, and the average values were used to calculatethe percent elongation to break: percent elongation=[(Lf−Lo)/Lo]×100.The tensile modulus (M) was calculated as the slope of the initiallinear portion of the stress-strain curve; the units of modulus arepounds per square inch or psi. The tensile strength (TS) was calculatedfrom the peak load and the original cross-sectional area: tensilestrength=peak load divided by the original cross-sectional area; theunits of tensile strength are psi. Toughness was calculated from theenergy to break and the original volume of the sample: toughness=energyto break divided by the original sample volume; the units of toughnessare in-lbs/in3. The elongation to break (ETB) was also recorded as thepercent strain at break.

PQ1 uptake (PQ1) was measured chromatographically. The HPLC wascalibrated using a series of standard PQ1 solutions havingconcentrations 2, 4, 6, 8, 12 and 15 μg/mL. Lenses were placed intopolypropylene contact lens cases with 3 mL of Optifree Replenish orsimilar lens solution (PQ1 concentration=10 micrograms/mL) which iscommercially available from Alcon. A control lens case, containing 3 mLof solution, but no contact lens was also prepared. The lenses andcontrol solutions were stored at room temperature for 72 hours. 1 mL ofsolution was removed from each of the samples and controls and mixedwith trifluoroacetic acid (10 μL). The analysis was conducted usingHPLC/ELSD and a Phenomenex Luna C₅ (4.6 mm×5 mm; 5 μm particle size)column with the following equipment and conditions: Agilent 1200 HPLC orequivalent with an ELSD operating at T=100° C., Gain=12, Pressure=4.4bar, Filter=3 s; ELSD parameters may vary from instrument to instrument;using mobile phase A of water (0.1% TFA) and mobile phase B ofacetonitrile (0.1% TFA), a column temperature of 40° C. and an injectionvolume of 100 μL. An elution profile was used and listed in Table C. Acalibration curve was created by plotting the peak area value as afunction of the concentration of the PQ1 standard solutions. Theconcentration of PQ1 in a sample was then calculated by solving thequadratic equation representing the calibration curve. Three lenses wererun for each analysis, and the results were averaged. PQ1 uptake wasreported as the percentage loss of PQ1 after soak with lens compared tothe PQ1 present in the control without lens.

TABLE C HPLC Elution Profile Time Flow Rate (minutes) % A % B (mL/min)0.00 100 0 1.2 1.00 100 0 1.2 5.00 0 100 1.2 8.50 0 100 1.2 8.60 100 01.2 11.00 100 0 1.2

The amount of cholesterol absorbed by a contact lens was determined by aLC-MS method (lipids). Lenses were soaked in a cholesterol solution andthen extracted with dichloromethane. The dichloromethane extract wasevaporated and reconstituted with a heptane/isopropanol mixture withsubsequent analysis by LC-MS. The results were reported as micrograms ofcholesterol per lens. A deuterated cholesterol internal standard wasused to improve accuracy and precision of the method.

A cholesterol stock solution was prepared by placing 15.0±0.5 milligramsof cholesterol into a wide-mouth 10 mL glass volumetric flask followedby dilution with isopropanol.

A cholesterol soak solution was prepared by placing 0.430±0.010 grams oflysozyme (purity=93%), 0.200±0.010 grams of albumin, and 0.100±0.010grams of β-lactoglobulin into a 200 mL glass volumetric flask, addingapproximately 190 milliliters of PBS to the flask, and swirling todissolve the contents. 2 Milliliters of the cholesterol stock solutionwas then added and diluted to volume with PBS. The volumetric flask wascapped and shaken well. The concentration of the cholesterol soaksolution was approximately 15 μg/mL. Note: The mass of these componentsmay be adjusted to account for lot-to-lot purity variability so that thetarget concentrations can be achieved.

Six contact lenses were removed from their packages and blotted withlint-free paper towels to remove excess packing solution. The lenseswere placed into six separate 8 mL glass vials (one lens per vial), and3.0 mL of the cholesterol soak solution was added to each vial. Thevials were capped and placed into a New Brunswick Scientificincubator-shaker for 72 hours at 37° C. and 100 rpm. After incubation,each lens was rinsed three times with PBS in 100 mL beakers and placedinto a 20-mL scintillation vial.

To each lens-containing scintillation vial, 5 mL of dichloromethane and100 μL of the internal standard solution were added. After a minimum of16 hours of extraction time, the supernatant liquid was transferred intoa 5 mL disposable glass culture tube. The tube was placed into theTurbovap and the solvent completely evaporated. Place 1 mL of thediluent into the culture tube and re-dissolve the contents. Theaforementioned diluent was a 70:30 (v/v) mixture of heptane andisopropanol. The diluent was also the mobile phase. The resultingsolution was carefully transferred into an autosampler vial and readyfor LC-MS analysis.

An internal standard stock solution was prepared by weighingapproximately 12.5±2 mg of deuterated cholesterol(2,2,3,4,4,6-d6-cholesterol) in a 25 mL volumetric flask followed bydilution with the diluent. The concentration of the internal standardstock solution was approximately 500 μg/mL.

An internal standard solution was prepared by placing 1.0 mL of theinternal standard stock solution in a 50 mL volumetric flask followed bydilution to volume with diluent. The concentration of this intermediateinternal standard solution is approximately 10 μg/mL.

A reference standard stock solution was prepared by weighingapproximately 50±5 mg of cholesterol in a 100 mL volumetric flaskfollowed by dilution with diluent. The concentration of the cholesterolin this reference stock solution is approximately 500 μg/mL.

Working standard solutions were then made according to Table D byplacing the appropriate amount of standard solutions into the listed 25mL, 50 mL or 100 mL volumetric flasks. After the standard solutions wereadded to the volumetric flasks, the mixture was diluted to volume withdiluent and swirled well.

TABLE D Working Standard Solution Formulations Volume Volume ofApproximate Working of Internal Reference Final Cholesterol StandardStandard Standard Stock Volume Concentration Name Solution (mL) Solution(μL) (mL) (μg/mL) Std 1 10 20 100 0.10 Std 2 5 25 50 0.25 Std 3 5 50 500.50 Std 4 5 100 50 1.00 Std 5 2.5 125 25 2.50 Std 6 2.5 250 25 5.00

The following LC-MS analysis was performed: Make 6 injections of the“Std4” to evaluate system suitability. The RSD % of the peak areas forthe working standards and the internal standards must be <5% and RSD (%)of their peak area ratios must be <7% to pass system suitability. Injectworking standards 1-6 to create a calibration curve. The square of thecorrelation coefficient (r²) must be >0.99. Inject test samples followedby a bracketing standard (Std4). The peak area ratio of the bracketingstandard must be within +10% of the averaged peak area ratio from thesystem suitability injections.

A calibration curve was constructed by plotting the peak area ratio(reference std/internal std) value that corresponds to the concentrationof each working standard solution. The concentration of cholesterol insample is calculated by solving a quadratic equation. Typical equipmentand their settings for the LC-MS analysis are listed below and shown inTables E and F. The values for the instrument tune parameters may changeeach time the mass spectrometer is tuned.

Turbovap Conditions:

-   -   Temperature: 45° C.    -   Time: 30 minutes or more to dryness    -   Gas: nitrogen @ 5 psi    -   HPLC Conditions:    -   HPLC: Thermo Accela HPLC Instrument or equivalent    -   HPLC Column: Agilent Zorbax NH2 (4.6 mm×150 mm; 5 μm particle        size)    -   Mobile Phase: 70% heptane and 30% isopropanol    -   Column Temperature: 30° C.    -   Injection Volume: 25 μL    -   Flow Rate: 1000 μL/min

TABLE E Mass Spectrometry Conditions Thermo Finnigan TSQ Quantum UltraMS Settings Value Ionization APCI Polarity Positive Scan type SIM APCIprobe position D Mass (m/z) of Reference Standards 369.2 Mass (m/z) ofInternal Standards 375.3 Mass width (m/z)  1.0 Scan time (s)   0.10 Datatype centroid Peak Width Q3 (FWHM)   0.40 Skimmer Offset (V)  10  

TABLE F Tune Parameters Instrument Tune Parameters Value DischargeCurrent (arbitrary units):  20 Capillary temperature (° C.): 240Vaporizer Temperature (° C.): 500 Tube lens offset (V):  68 Sheath gaspressure (arbitrary units):  20 Auxiliary gas flow (arbitrary units): 15

The amount of lysozyme uptake by a contact lens was measured by aHPLC-UV method. Lysozyme uptake was determined as the difference oflysozyme content in phosphate-buffered saline solution (PBS) beforecontact lenses are immersed and the concentration in the test solutionafter 72 hours of lens immersion at 37° C.

A lysozyme soak solution was prepared by placing 0.215±0.005 grams oflysozyme (purity=93%) into a 100 mL volumetric flask followed by adding50 mL of PBS to dissolve the lysozyme by swirling followed by dilutionto volume with PBS. The resulting lysozyme soak solution wasfiltered/sterilized using a Millipore Stericup filtration device. Theconcentration of the lysozyme soak solution is approximately 2000 μg/mL.The mass of lysozyme may be adjusted to account for lot-to-lot purityvariability so that a 2000 μg/mL concentration can be achieved.

Three contact lenses were removed from their packages and blotted withlint-free paper towel to remove excess packing solution. The lenses wereplaced into three separate 8 mL glass vials (one lens per vial). 1.5 mLof the lysozyme soak solution was added to each vial. The vials werecapped and inspected to ensure each lens was completely immersed in thesoak solution. As control samples, 1.5 mL of lysozyme soak solution wereadded into three separate 8 mL glass vials. The samples were thenincubated on a New Brunswick Scientific incubator-shaker for 72 hours at37° C. and 100 rpm.

A diluent was prepared by mixing 900 mL water, 100 mL acetonitrile and 1mL trifluoroacetic acid into a 1 L glass bottle.

A lysozyme stock solution was prepared by placing 0.240±0.010 grams oflysozyme (purity=93%) into a 100 mL volumetric flask followed bydilution to volume with diluent. The concentration of the lysozyme stocksolution is approximately 2200 μg/mL.

As shown in Table G, a series of working standard solutions was preparedby mixing the appropriate amounts of lysozyme stock solution withdiluent using 5 mL volumetric flasks.

TABLE G Working Standards Working Volume Final Approximate Standard ofStock Volume Lysozyme Name Solution (mL) (mL) Concentration (μg/mL) Std1 1.135 5 500 Std 2 1.815 5 800 Std 3 2.725 5 1200 Std 4 3.635 5 1600Std 5 4.540 5 2000 Std 6 (stock) — — 2200

A 10% (v/v) solution was prepared by adding 1 mL of trifluoroacetic acidinto a 10 mL glass volumetric flask followed by dilution with HPLCwater. Samples for HPLC-UV analysis were prepared as follows: (1) byplacing 1000 μL of test sample and 10 μL of the 10% TFA solution into anautosampler vial or (2) by placing 1000 μL of reference standard and 10μL of reference standard diluent into an autosampler vial.

The analysis involved the following steps: Perform 6 injections of the“Std4” to evaluate system suitability. The RSD % of the peak areas andretention times must be <0.5% to pass system suitability. Inject workingstandards 1-6 to create a calibration curve. The square of thecorrelation coefficient (r²) must be >0.99. Inject test samples followedby a bracketing standard (Std4). The peak area of the bracketingstandard must be +1% of the averaged peak areas from the systemsuitability injections.

A calibration curve was constructed by plotting the peak area value thatcorresponds to the concentration of each lysozyme working standardsolution. The concentration of lysozyme in the test samples wascalculated by solving a linear equation. Typical equipment and theirsettings are listed below or shown in Table H.

-   -   Instrument: Agilent 1200 HPLC with UV detection (or equivalent        HPLC-UV)    -   Detection: UV @ 280 nm (5 nm bandwidth)    -   HPLC Column: Phenomenex Luna C₅ (50×4.6 mm) or Agilent PLRP-S        (50×4.6 mm)    -   Mobile Phase A: H2O (0.1% TFA)    -   Mobile Phase B: Acetonitrile (0.1% TFA)    -   Column Temperature: 40° C.    -   Injection Volume: 10 μL

TABLE H HPLC Run Conditions Time Flow Rate (minutes) % A % B (mL/min)0.0 95 5 1.2 4.0 5 95 1.2 4.1 95 5 1.2 6.5 95 5 1.2

Haze may be measured by placing a hydrated test lens in borate bufferedsaline in a clear glass cell at ambient temperature above a flat blackbackground, illuminating from below with a fiber optic lamp(Dolan-Jenner PL-900 fiber optic light with 0.5″ diameter light guide)at an angle 66° normal to the lens cell, and capturing an image of thelens from above, normal to the lens cell with a video camera (DVC1300C:19130 RGB camera or equivalent equipped with a suitable zoomcamera lens) placed 14 mm above the lens holder. The background scatteris subtracted from the scatter of the test lens by subtracting an imageof a blank cell with borate buffered saline (baseline) using EPIX XCAP V3.8 software. The value for high end scatter (frosted glass) is obtainedby adjusting the light intensity to be between 900 to 910 meangrayscale. The value of the background scatter (BS) is measured using asaline filled glass cell. The subtracted scattered light image isquantitatively analyzed, by integrating over the central 10 mm of thelens, and then comparing to a frosted glass standard. The lightintensity/power setting was adjusted to achieve a mean grayscale valuein the range of 900-910 for the frosted glass standard; at this setting,the baseline mean grayscale value was in the range of 50-70. The meangrayscale values of the baseline and frosted glass standard are recordedand used to create a scale from zero to 100, respectively. In thegrayscale analysis, the mean and standard deviations of the baseline,frosted glass, and every test lens was recorded. For each lens, a scaledvalue was calculated according to the equation: scaled value equals themean grayscale value (lens minus baseline) divided by the mean grayscalevalue (frosted glass minus baseline) times by 100. Three to five testlenses are analyzed, and the results are averaged.

The invention is now described with reference to the following examples.Before describing several exemplary embodiments of the invention, it isto be understood that the invention is not limited to the details ofconstruction or process steps set forth in the following description.The invention is capable of other embodiments and of being practiced orbeing carried out in various ways.

The following abbreviations will be used throughout the Examples andhave the following meanings:

-   -   BC: back curve plastic mold    -   FC: front curve plastic mold    -   RMM: reactive monomer mixtures    -   NVP: N-vinylpyrrolidone (Acros or Aldrich)    -   DMA: N, N-dimethylacrylamide (Jarchem)    -   MMA: methyl methacrylate    -   HEMA: 2-hydroxyethyl methacrylate (Bimax)    -   MAA: methacrylic acid (Acros)    -   ACA1: 3-acrylamidopropanoic acid    -   Q Salt or METAC: 2-(methacryloyloxy)ethyl trimethylammonium        chloride    -   CBT: 1-Propanaminium,        N-(2-carboxyethyl)-N,N-dimethyl-3-[(1-oxo-2-propen-1-yl)amino]-,        inner salt; carboxybetaine; CAS 79704-35-1    -   SBT: 1-Propanaminium,        N,N-dimethyl-N-[3-[(1-oxo-2-propen-1-yl)amino]propyl]-3-sulfo-,        inner salt; sulfobetaine; CAS 80293-60-3    -   PBT: 3,5-Dioxa-8-aza-4-phosphaundec-10-en-1-aminium,        4-hydroxy-N,N,N-trimethyl-9-oxo, inner salt, 4-oxide (9CI);        phosphobetaine; CAS 163674-35-9    -   MPC: 3,5,8-trioxa-4-phosphaundec-10-en-1-aminium,        4-hydroxy-N,N,N,10-tetramethyl-9-oxo, inner salt, 4-oxide; CAS        67881-98-5    -   Blue HEMA:        1-amino-4-[3-(4-(2-methacryloyloxy-ethoxy)-6-chlorotriazin-2-ylamino)-4-sulfophenylamino]anthraquinone-2-sulfonic        acid, as described in U.S. Pat. No. 5,944,853    -   PVP: poly(N-vinylpyrrolidone) (ISP Ashland)    -   EGDMA: ethylene glycol dimethacrylate (Esstech)    -   TEGDMA: tetraethylene glycol dimethacrylate (Esstech)    -   TMPTMA: trimethylolpropane trimethacrylate (Esstech)    -   Tegomer V-Si 2250: diacryloxypolydimethylsiloxane (Evonik)    -   CGI or Irgacure 819:        bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide (BASF or Ciba        Specialty Chemicals)    -   CGI or Irgacure 1870: blend of        bis(2,6-dimethoxybenzoyl)-2,4,4-trimethyl-pentylphosphineoxide        and 1-hydroxy-cyclohexyl-phenyl-ketone (BASF or Ciba Specialty        Chemicals)    -   mPDMS: mono-n-butyl terminated monomethacryloxypropyl terminated        polydimethylsiloxane (M_(n)=800-1000 g/mol) (Gelest)    -   ac-PDMS: bis-3-acryloxy-2-hydroxypropyloxypropyl        polydimethylsiloxane    -   HO-mPDMS: mono-n-butyl terminated        mono-(2-hydroxy-3-methacryloxypropyl)-propyl ether terminated        polydimethylsiloxane (M_(n)=400-1500 g/mol) (Ortec or        DSM-Polymer Technology Group)    -   SiMAA: 2-propenoic acid,        2-methyl-2-hydroxy-3-[3-[1,3,3,3-tetramethyl-1-[(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl        ester (Toray), also known as        3-(3-(1,1,1,3,5,5,5-heptamethyltrisiloxan-3-yl)propoxy)-2-hydroxypropyl        methacrylate or        2-hydroxy-3-[3-methyl-3,3-di(trimethylsiloxy)silylpropoxy]-propyl        methacrylate    -   mPEG 950: polyethylene glycol methyl ether methacrylate        (Aldrich) (CAS 26915-72-0; M_(n)=950 g/mol) which may be        purified by crystallization from diethyl ether    -   D3O: 3,7-dimethyl-3-octanol (Vigon)    -   DIW: deionized water    -   IPA: isopropyl alcohol    -   PG: propylene glycol    -   BAGE: Boric Acid Glycerol Ester (molar ratio of boric acid to        glycerol was 1:2) 299.3 grams (mol) of glycerol and 99.8 grams        (mol) of boric acid were dissolved in 1247.4 grams of a 5% (w/w)        aqueous EDTA solution in a suitable reactor and then heated with        stirring to 90-94° C. under mild vacuum (2-6 torr) for 4-5 hours        and allowed to cool down to room temperature.    -   EDTA: ethylenediaminetetraacetic acid    -   Norbloc:        2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H-benzotriazole        (Janssen)    -   Borate Buffered Packing Solution: 18.52 grams (300 mmol) of        boric acid, 3.7 grams (9.7 mmol) of sodium borate decahydrate,        and 28 grams (197 mmol) of sodium sulfate were dissolved in        enough deionized water to fill a 2 liter volumetric flask.    -   TL03 Lights: Phillips TLK 40W/03 or equivalents    -   DMBAPO: bis(2,6-dimethoxybenzoyl)-2,4,4-trimethylpentyl        phosphine oxide    -   BAPO-OH: bis(mesitoyl)phosphinic acid or        hydroxyphosphanediyl)bis(mesitylmethanone); see Macromol. Rapid        Commun. 2015, 36, 553-557.

-   -   HCPK: 1-hydroxy-cyclohexyl-phenyl-ketone    -   mPEG475: polyethylene glycol methyl ether methacrylate (Aldrich)        (Mn=475 g/mol)    -   nBMA: n-butyl methacrylate    -   DMF: N,N-dimethylformamide    -   Fluorescein Acrylamide:        N-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-5-yl)acrylamide        (Polysciences)

-   -   Fluorescein Methacrylamide:        N-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-5-yl)methacrylamide        (Polysciences)

-   -   TPME: tripropylene glycol methyl ether    -   TEGDA: tetraethylene glycol diacrylate    -   DCM: Dichloromethane    -   KI: Potassium iodide    -   NaI: Sodium iodide:    -   Tert-BuOH or t-BuOH: tertiary butanol    -   Et3N: triethylamine    -   MeLi: methyl lithium    -   CDI: carbonyldiimidazole    -   TFA or CF3COOH: trifluoroacetic acid    -   NaBr: sodium bromide    -   THF: tetrahydrofuran    -   Na2CO3: sodium bicarbonate    -   Na2SO4: sodium sulfate    -   HMPA: hexamethylphosphoramide    -   NaOH: sodium hydroxide    -   NMR: nuclear magnetic resonance spectroscopy    -   TMS: tetramethylsilane    -   NT: not tested    -   WC: water content (wt. %)    -   EC Dk: edge-corrected oxygen gas permeability (barrers)    -   M: modulus (psi)    -   TS: tensile strength (psi)    -   ETB: elongation to break (%)    -   RI: refractive index    -   Kruss DCA (adv): advancing dynamic contact angle    -   Sessile Drop: advancing contact angle

Examples 1-3

Reactive monomer mixtures (representative of the first reactivecomposition described above) were formed by mixing the reactivecomponents listed in Table 1. These formulations were filtered through a3 μm filter using a heated or unheated stainless steel or glass syringedepending on viscosity and degassed by applying vacuum (about 40 mm Hg)at ambient temperature for about 10 minutes. With a nitrogen gasatmosphere and about 0.5 percent oxygen gas, 75 μL of the reactivemixture were dosed into the FC. The BC was then placed onto the FC. Apallet containing eight lens mold assemblies was irradiated for 10minutes at 60° C. or at 70° C. using 435 nm lights having intensity of 6mW/cm². The light source was about two inches above the pallets. Thelenses may be stored protected from any additional exposure to light andde-molded and hydrated at later times.

Working under yellow lights and limiting general exposure to light(e.g., by wrapping containers with aluminum foil), the lenses weremanually de-molded with most lenses adhering to the FC and released bysuspending about 64 lenses in about one liter of 70 percent IPA forabout one or two hours, sometimes overnight, followed by washing twotimes with 70 percent IPA, two times with deionized water, and finallystored in deionized water in the refrigerator in aluminum foil coveredcontainers for subsequent grafting experiments. Each washing step lastedabout 30 minutes. A person of ordinary skill recognizes that the exactlens release process can be varied depending on the lens formulation andmold materials, regarding the concentrations of the aqueous isopropanolsolutions, the number of washings with each solvent, and the duration ofeach step. The purpose of the lens release process is to release alllenses without defects and transition from diluent swollen networks tothe deionized water or packaging solution swollen hydrogels. The lenseswere equilibrated in borate buffered packing solution for at least 24hours, transferred into vials, and subsequently sterilized byautoclaving at 122° C. for 30 minutes. The physical and mechanicalproperties of the sterile lenses were measured and listed in Table 2.

TABLE 1 Weight Percent Weight Percent Component Examples 1-2 Example 3mPDMS 31 0 SiMAA 28 0 DMA 24 0 HEMA 6 93.31 MAA 0 0.7 PVP K90 7 0 TEGDMA1.64 0 EGDMA 0 0.9 TMPTMA 0 0.09 Norbloc 2 0 CGI 819 0.34 5 Blue-HEMA0.02 0 Σ RMM Components 100 100 Diluent D3O 30 0 Diluent BAGE 0 50 CureTemperature (° C.) 60 70

TABLE 2 Kruss Sessile Diameter WC EC Dk M TS ETB DCA Drop Lipids Example(mm) (Wt. %) (barrers) (psi) (psi) (%) RI (adv) (°) (μg/lens) Ex 1 13.540 94 123 (12) 96 (9) 169 (32) 1.4209 NT 45 (6) 3.9 (0.5) Ex 2 13.0 36.3102 104 (7)  106 (21) 185 (35) 1.4213 46 (6) 70 (8) 2.7 (0.3) Ex 3 11.361 NT NT NT NT NT NT NT NT

The hydrogels of examples 1-3 (representative of crosslinked substratenetworks of the invention) were used in the following graftingexperiments. These substrate networks were stored in the dark. Thediameters and water contents of examples 1-3 were used to calculate thepercent change in diameters and water contents of the grafted hydrogels.

Examples 4-27

Generally, in a glove box with a nitrogen gas atmosphere and less than0.2 percent oxygen gas, the grafting experiments were carried out in 100mL glass jars in which lenses were suspended in a reactive monomermixture (representative of the second reactive composition of theinvention) at a concentration of one lens per 1-5 mL of reactive monomermixture. The suspensions were first degassed for 15-30 minutes usingvacuum (about 40 torr) and then purged with nitrogen gas aeration, thejars capped, and then their contents equilibrated at 60-65° C. on ashaker bath for about 90 minutes. The caps were replaced by clearplastic covers, and the jars irradiated with TL03 lights (wavelength380-470 nm; peak 420 nm). After irradiation, the lenses were removed andwashed two times in 70% (v/v) aqueous IPA, two times with deionizedwater, and two times with borate buffered packing solution. The lenseswere stored in vials. After about two days of equilibration, the lenseswere inspected, sterilized by autoclaving at 122° C. for 30 minutes. Thephysical and mechanical properties of the sterile lenses were measured.

In some experiments, the light intensity was reduced by placing 1-6sheets of paper (Berkshire DUR670) between the light source and the jarsbeing irradiated. For all experiments, the actual light intensity wasmeasured with an ITL 1400 radiometer and sometimes reported as a rangeif variations were detected.

Table 3 lists various reactive monomer mixtures and grafting conditionsused to create grafted polymeric networks on the lenses made in Examples1-3. mPEG950 macromer was purified by dissolution in refluxing diethylether and crystallization upon cooling to 4° C. thereby removing theinhibitor. Tables 4-6 list the physical and mechanical properties of thecontact lenses made from such grafted networks.

The formation of grafted polymeric networks was consistent with the lensdry weight gains, the lens diameter increases, and the changes in watercontent and oxygen permeability (Dk) depending on the hydrophilicity orhydrophobicity of the monomers in the grafting reactive monomermixtures. Examples 4, 5, and 10 exhibited lysozyme uptakes of 2,773(±30) μg/lens, 2,806 (+16) μg/lens, and 2,231 (+31) μg/lensrespectively, and examples 5 and 10 exhibited PQ1 uptakes of 71.2% and64.4% respectively, because of the grafting of carboxylic acid monomers.The grafting reactive monomer mixture of Example 4 included acrosslinking agent.

TABLE 3 Light Cure Equilibration Solvent Intensity Time RMM Composition% (w/v) Time (min) (v/v) (mW/cm²) (min) Using Example 1 as the substratenetwork containing MAPO groups: Ex 4 5% HEMA, 0.5% MMA, 90 50:500.105-0.108 30 0.05% EGDMA 1 lens/5 mL PG:DIW Ex 5 1.25% MAA 90 50:500.105-0.108 40 1 lens/5 mL PG:DIW Ex 6 5% MPC 90 50:50 0.280-0.320 40 1lens/5 mL PG:DIW Ex 7 5% CBT 90 50:50 0.280-0.320 40 1 lens/5 mL PG:DIWEx 8 5% PBT 90 50:50 0.280-0.320 40 1 lens/5 mL PG:DIW Ex 9 5% SBT 9050:50 0.280-0.320 40 1 lens/5 mL PG:DIW Using Example 2 as the substratenetwork containing MAPO groups: Ex 10 5% ACA1 60 50:50 2.4 30 1 lens/2.5mL PG:DIW Ex 11 5% DMA 60 90:10 1 lens/2.5 mL PG:DIW Ex 12 10% MMA 6050:50 90 1 lens/2.5 mL PG:DIW Ex 13 50% NVP 60 50:50 1 lens/2.5 mLPG:DIW Ex 14 10% purified mPEG950 90-120 50:50 0.89 30 1 lens/2 mLPG:DIW Ex 15 50:50 45 PG:DIW Ex 16 50:50 60 PG:DIW Ex 17 50:50 75 PG:DIWEx 18 50:50 90 PG:DIW Ex 19 50:50 0.41/0.81 60@0.41/ PG:DIW 30@.81   Ex20 50:50 60@0.41/ PG:DIW 60@0.81  Using Example 3 as the substratenetwork containing MAPO groups: Ex 21 5% DMA 90-120 50:50 2.4 30 PG:DIWEx 22 100% NVP; note cure 1 lens/2.5 mL None 2.4 120 temperature = 65°C. Ex 23 10% mPEG950 50:50 2.4 60 PG:DIW Ex 24 10% MMA; note cure 50:502.4 90 temperature = 65° C. PG:DIW Ex 25 5% ACA1 50:50 2.4 60 PG:DIW Ex26 5% MPC 50:50 0.3 60 PG:DIW Ex 27 12% SiMAA; note cure 45:45:10 2.4120 temperature = 65° C. PG: n-propanol:DIW

TABLE 4 Lens Kruss Sessile Weight DM WC EC Dk M TS ETB DCA Drop LipidsGain (%) (mm) (wt %) (barrers) (psi) (psi) (%) RI (adv) (°) (μg/lens) Ex1 13.5 40 94 123 (12) 96 (9)  169 (32) 1.4209 NT 45 (6) 3.9 (0.5) Ex 433.7 15.8 52 62 116 (19) 80 (10) 106 (8)  1.4083 NT 65 (5) 4.5 (0.3) Ex5 22.4 16.7 66 47 155 (14) 43 (22)  41 (18) 1.3920 NT NT 3.0 (1.5) Ex 610.5 14.9 48 66  96 (10) 91 (16) 158 (27) 1.4077 32 (8) 29 (2) 1.9 (0.2)Ex 7 3.9 14.5 44 77 96 (6) 69 (14) 130 (20) 1.4149 52 (3) 50 (6) 3.9(0.7) Ex 8 2.5 14.3 45 88 108 (4)  81 (11) 134 (29) 1.4141 47 (5) 44 (4)4.3 (0.5) Ex 9 1.2 14.3 42 90 103 (4)  94 (27)  99 (18) 1.4183 48 (9) 42(4) 3.9 (0.3)

TABLE 5 Lens Kruss Sessile Weight DM WC EC Dk M TS ETB DCA Drop LipidsGain (%) (mm) (wt %) (barrers) (psi) (psi) (%) RI (adv) (°) (μg/lens) Ex2 13.0 36.3 102 104 (7) 106 (21) 185 (35) 1.4213 46 (6) 70 (8) 2.7 (0.3)Ex 10 11.1 15.4 60 68 109 (8) 24 (9)  81 (12) NT 48 (5) NT 2.9 (0.9) Ex11 7.4 13.9 49 81  89 (8)  77 (26) 137 (39) NT 49 (6) NT NT Ex 12634 >18 31 NT NT NT NT NT NT NT NT Ex 13 21.8 15.3 56 NT NT NT NT NT NTNT NT Ex 14 0.9 13.3 41 100 102 (23)  97 (25) 179 (28) 1.4196  39 (14)NT 5.42 Ex 15 4.8 13.6 43 98 105 (8) 98 (9) 167 (23) 1.4100 54 (1) NT3.7 Ex 16 5.8 13.8 44 90  98 (4) 104 (19) 181 (31) 1.4133  87 (13) NT3.77 Ex 17 25.6 14-15 57 57  91 (18)  58 (44)  82 (51) 1.3972  48 (16)NT 3.47 Ex 18 29.5 15-16 50 61 124 (6)  61 (16)  86 (30) 1.3944 54 (3)NT 3.17 Ex 19 1.3 13.8 44 99  93 (8) 104 (43) 180 (65) 1.4132 NT NT NTEx 20 6.4 14.3 47 86  90 (7)  98 (29) 177 (50) 1.4085 59 (2) NT 3.54

TABLE 6 Lens DM WC Weight DM Increase WC Change EC Dk Gain (%) (mm) (%)(%) (%) (barrers) Ex 3 NT 11.3 NT 61 NT  NT* Ex 21 29.8 13.0 15.5 66 8.2NT Ex 22 20 11.7 3.5 69.3 13.6 NT Ex 23 188 17.6 56 76.8 25.9 NT Ex 24458 16.4 >45 43.8 (28.2) NT Ex 25 36.8 15.4 37 89 45.9 NT Ex 26 26 12.813.5 66 8.2 NT Ex 27 233 14.1 24 35.5 (41.8) 58.5 *Lenses with similarformulations such as etafilcon typically exhibit Dk between 25 and 30barrers.

Examples 27-31

Reactive monomer mixtures were formed by mixing the reactive componentslisted in Table 7. These formulations were filtered through a 3 μmfilter and degassed. In a glove box with a nitrogen gas atmosphere andless than 0.2 percent oxygen gas, about 75-100 μL of the reactivemixture were dosed using an Eppendorf pipet at room temperature into theFC. The BC was then placed onto the FC. The molds were equilibrated fora minimum of twelve hours in the glove box prior to dosing. A platecontaining about four pallets, each pallet containing eight lens moldassemblies, was transferred into an adjacent glove box maintained at 65°C., and the lenses were cured from the top for 15 minutes using 435 nmlights having intensity of 4 mW/cm². The light source was about sixinches above the trays.

Working under yellow lights and limiting general exposure to additionallight exposure (e.g., by wrapping containers with aluminum foil, etc.).The lenses were manually de-molded with most lenses adhering to the FCand released by suspending about 64 lenses in about one liter of 70percent IPA for about one or two hours, sometimes overnight, followed bywashing two times with 70 percent IPA, two times with deionized water,and finally stored in deionized water in the refrigerator in aluminumfoil covered containers. Each washing step lasted about 30 minutes. Somelenses were equilibrated in borate buffered packing solution for atleast 24 hours, transferred into vials, and subsequently sterilized byautoclaving at 122° C. for 30 minutes. The physical and mechanicalproperties of the sterile lenses were measured and listed in Table 8.

In a glove box with a nitrogen gas atmosphere and less than 0.2 percentoxygen gas, lenses from example 27 were suspended in 100 mL glass jarsat a concentration of one lens/2 mL of reactive monomer mixture. Thereactive monomer mixture was a solution of 5% (v/v) HEMA, 0.5% (v/v)MAA, and 0.05% (v/v) EGDMA in 50:50 (v/v) propylene glycol:deionizedwater solution. The suspensions were first degassed for 15-30 minutesusing vacuum (about 40 torr) and then purged with nitrogen gas aeration,the jars capped, and then their contents equilibrated at 60° C. on ashaker bath for 90-120 minutes. The caps were replaced by clear plasticcovers, and the jars irradiated with TL03 lights using paper filters toreduce the intensity to 0.107 mW/cm². Jars were removed after 15 minutes(example 28), 30 minutes (example 29), 45 minutes (example 30), and 60minutes (example 31) to monitor the rate of grafting. After irradiation,the lenses were removed and washed two times in 70% (v/v) aqueous IPA,two times with deionized water, and two times with borate bufferedpacking solution. The lenses were stored in vials. After about two daysof equilibration, the lenses were inspected, sterilized by autoclavingat 122° C. for 30 minutes. The physical and mechanical properties of thesterile lenses were measured and listed in Table 8.

TABLE 7 Weight Percent Component Example 27 OH-mPDMS (n = 4) 10 OH-mPDMS(n = 15) 50 ac-PDMS Tegomer V Si 2250 10 DMA 10 HEMA 10.73 PVP K90 7Norbloc 1.75 Blue-HEMA 0.02 CGI 819 0.5 Σ RMM Components 100 Diluent D3O23

TABLE 8 Lens Sessile Lysozyme PQ1 Weight DM WC EC Dk M TS ETB DropLipids Uptake Uptake Gain (%) (mm) (Wt %) (barrers) (psi) (psi) (%) RI(°) (μg/lens) (μg/lens) (%) Ex 27 — 12.07 23.4 169 NT NT NT NT NT NT NTNT Ex 28 21.2 13.7 37.1 154 186 80 67 1.4204 74.7 9.41 704 56 Ex 29 53.815.5 47.4 97 203 65 55 1.4103 58.5 10.99 2796 73 Ex 30 99.8 17.3 51.9 60230 65 48 1.4050 52.1 11.31 2915 >80 Ex 31 128.1 18.6 53.8 54 259 154 891.4019 35.1 8.84 2933 >80

The formation of grafted networks was consistent with the increases inlens dry weight, lens diameter, water content, lysozyme uptake, and PQ1uptake as a function of grafting time as well as the downward trend inedge corrected Dk and sessile drop wettability.

Example 32

A reactive monomer mixture was formed by mixing the reactive componentslisted in Table 9. This formulation was filtered through a 3 μm filterusing a heated or unheated stainless steel or glass syringe and degassedby applying vacuum (about 40 mm Hg) at ambient temperature for about 10minutes. With a nitrogen gas atmosphere and about 0.2 percent oxygengas, 75 μL of the reactive mixture were dosed into the FC. The BC wasthen placed onto the FC. A plate containing about four pallets, eachpallet containing eight lens mold assemblies, was transferred into anadjacent glove box maintained at 60-65° C., and the lenses were curedfrom the top for 12 minutes using 435 nm LEDs having intensity of 4mW/cm². The light source was about six inches above the trays. Thelenses were stored protected from any additional exposure to light andde-molded and hydrated at later times.

Working under yellow lights and limiting general exposure to light(e.g., by wrapping containers with aluminum foil), the lenses weremanually de-molded with most lenses adhering to the FC and released bysuspending about 64 lenses in about one liter of 70 percent IPA forabout one or two hours, followed by washing two times with 70 percentIPA, two times with deionized water, and finally stored in deionizedwater in the refrigerator in covered containers for subsequent graftingexperiments. Each washing step lasted about 30 minutes. After one day ofequilibration, the lenses were inspected and sterilized by autoclavingat 122° C. for 30 minutes. The lenses equilibrated 3-4 days aftersterilization, and then, the physical and mechanical properties of thesterile lenses were measured. A person of ordinary skill recognizes thatthe exact lens release process can be varied depending on the lensformulation and mold materials, regarding the concentrations of theaqueous isopropanol solutions, the number of washings with each solvent,and the duration of each step. The purpose of the lens release processis to release all lenses without defects and transition from diluentswollen networks to the deionized water or packaging solution swollenhydrogels.

25 Lenses were suspended in 50 mL of a 0.05% (w/v) methacrylic acidsolution of 50:50 (v/v) aqueous 1, 2-propylene glycol in a 100 mL glassjar and degassed for 15 minutes under reduced pressure (ca. 40 mm Hg)and purged with nitrogen gas aeration. The jar was capped andtransferred into glove box with a nitrogen gas atmosphere with less than0.2 percent oxygen gas and a temperature of 64° C. and equilibrated on ashaker (180 rpm) for 90 minutes. The temperature of the suspension wasthen 55° C. The cap was replaced by a clear plastic cover, and thesuspension was irradiated using 420 LEDs from the top having anintensity of 2 mW/cm² for 35 minutes while still being shaken. Afterirradiation, the lenses were removed and washed two times with deionizedwater and two times with borate buffered packing solution. The lenseswere stored in vials. After one day of equilibration, the lenses wereinspected and sterilized by autoclaving at 122° C. for 30 minutes. Thelenses were equilibrated 3-4 days after sterilization, and then, thephysical and mechanical properties of the sterile lenses were measured.Table 10 lists the physical and mechanical properties of the grafted andun-grafted lenses.

TABLE 9 Weight Percent Component Example 32 HEMA 4.65 NVP 52.76 TRIS19.97 TEGDMA 2.4 mPDMS 1000 19.86 Blue HEMA 0.02 Irgacure 819 0.34 Σ RMMComponents 100 Monomer Content in RMM 83 Ethanol 50 Ethyl Acetate 50 ΣDiluent Components 100 Diluent Content in RMM 17

TABLE 10 Lens Weight WC M TS ETB Toughness Sessile Ex 32 Gain (%) (wt.%) (psi) (psi) (%) (in-lb/in³) Drop Un-grafted — 36.9 (0.02) 101 (4) 143 (26) 271 (46) 187 (53) 91 (9) Lens Grafted Lens 30.3 66.7 (0.01) 169(12)  60 (18)  59 (13)  17 (12) 28 (2)

The formation of grafted networks was consistent with the increases inlens dry weight and equilibrium water content upon hydration as well asthe decrease in sessile drop wettability. Grafting methacrylic acid alsochanged the mechanical properties of the lenses.

Example 33

A reactive monomer mixture was formed by mixing the reactive componentslisted in Table 11. This formulation was filtered through a 3 μm filterusing a heated or unheated stainless steel or glass syringe and degassedby applying vacuum (about 40 mm Hg) at ambient temperature for about 10minutes. With a nitrogen gas atmosphere and about 0.2 percent oxygengas, 75 μL of the reactive mixture were dosed into the FC. The BC wasthen placed onto the FC.

A plate containing about four pallets, each pallet containing eight lensmold assemblies, was transferred into an adjacent glove box maintainedat 60-65° C., and the lenses were cured from the top and bottom for 15minutes using 435 nm lights having intensity of 4.5 mW/cm². The lightsources were about six inches above the trays. The lenses were storedprotected from any additional exposure to light and de-molded andhydrated at later times.

Working under yellow lights and limiting general exposure to light(e.g., by wrapping containers with aluminum foil), the lenses weremanually de-molded with most lenses adhering to the FC and released bysuspending about 64 lenses in about one liter of 70 percent IPA forabout one or two hours, followed by washing two times with 70 percentIPA, two times with deionized water, and finally stored in deionizedwater in the refrigerator in covered containers for subsequent graftingexperiments. Each washing step lasted about 30 minutes. A person ofordinary skill recognizes that the exact lens release process can bevaried depending on the lens formulation and mold materials, regardingthe concentrations of the aqueous isopropanol solutions, the number ofwashings with each solvent, and the duration of each step. The purposeof the lens release process is to release all of lenses without defectsand transition from diluent swollen networks to the deionized water orpackaging solution swollen hydrogels.

25 Lenses were suspended in 50 mL of a 5% (w/v) mPEG475 solution of50:50 (w/v) aqueous 1, 2-propylene glycol in a 100 mL glass jar anddegassed for 20 minutes under reduced pressure (ca. 40 mm Hg) and purgedwith nitrogen gas aeration. The jar was capped and transferred intoglove box with a nitrogen gas atmosphere with less than 0.2 percentoxygen gas and a temperature of 64-65° C. and equilibrated on a shaker(180 rpm) for 90 minutes. The temperature of the suspension was then54-55° C. The cap was replaced by a clear plastic cover, and thesuspension was irradiated using 420 LEDs from the top having anintensity of 1.45 mW/cm² for 40 minutes while still being shaken. Afterirradiation, the lenses were removed and washed two times with deionizedwater and two times with borate buffered packing solution. The lenseswere stored in vials. After one day of equilibration, the lenses wereinspected and sterilized by autoclaving at 122° C. for 30 minutes. Thelenses equilibrated 3-4 days after sterilization, and then, the physicalproperties of the sterile lenses were measured. Table 12 lists thephysical properties of the grafted and un-grafted lenses.

TABLE 11 Weight Percent Component Example 33 mPDMS 31 SiMAA 28 DMA 24HEMA 6 PVP K90 7 TEGDMA 1.64 Norbloc 1.84 BAPO-OH 0.5 Blue-HEMA 0.02 ΣRMM Components 100 Monomer Content in RMM 70 Diluent D30 100 DiluentContent in RMM 30

TABLE 12 Lens Weight WC Lens % Increase Ex 33 Gain (%) (wt. %) Diameter(mm) in Diameter Un-grafted Lens — 36.2 14.0 — Grafted Lens 9.53 43.414.9 6.43

The formation of grafted networks was consistent with the increases inlens dry weight, hydrated lens diameter and equilibrium water content.

Example 34

A reactive monomer mixture of 14.25 grams of nBMA, 75 milligrams ofEGDMA, and 75 milligrams of CGI 819 was prepared and degassed undervacuum (ca. 40 mm Hg) for 15 minutes. In a nitrogen gas atmosphere andabout 0.2 percent oxygen gas, 100 μL of the reactive mixture were dosedinto the FC. The BC was then placed onto the FC. A plate containingabout four pallets, each pallet containing eight lens mold assemblies,was transferred into an adjacent glove box maintained at 60° C., and thelenses were cured from the top and bottom for 15 minutes using 435 nmlights having intensity of 14 mW/cm². The light sources were about sixinches above the trays. The lenses were mechanically release and 30lenses were swollen in DMF to remove residual monomer and initiator. TheDMF was exchanged with fresh DMF one time.

A grafting solution was prepared by mixing 3 grams of DMA, 3 milligramsof fluorescein acrylamide[N-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-5-yl)acrylamide],and 27 grams of DMF. 5 Lenses were suspended in this grafting solutionin ajar and degassed under vacuum (ca. 40 mm Hg) for 25 minutes. The jarwas transferred into a glove box preheated to 65° C. and allowed toequilibrate for one hour before being irradiated from above by TL03light bulbs having an intensity of 3 mW/cm². The jar was swirled at 85rpm during the irradiation.

The grafted lenses were soaked in acetone to remove the DMF overnight.The grafted lenses were then soaked in fresh acetone for one hour,removed from suspension, and vacuum dried at room temperature for onehour. Seven un-grafted lenses were simultaneously taken through the sameDMF swelling and acetone exchange treatments and vacuum drying cycle.The un-grafted lenses were then further vacuum dried at 60° C. for 3hours. The grafted and un-grafted lenses were weighed and averagescalculated. The grafted lenses showed a dry weight increase of 32 weightpercent over the un-grafted lenses.

The dried lenses were subsequently suspended in about 500 mL of boratebuffered packing solution in ajar and rolled overnight. The hydratedgrafted and un-grafted lenses were weighed and averages calculated. Thegrafted lenses were uniformly yellow in color and stored in jars inborate buffered packing solution. The hydrated grafted lenses absorbedsignificantly more water than the un-grafted lenses. The water contentof the hydrated grafted lenses was 18 weight percent while the watercontent of the hydrated un-grafted lenses was 0.6 weight percent. Theformation of grafted networks was consistent with the increases in lensdry weight and equilibrium water content.

A hydrated grafted lens was staged and subjected to confocalfluorescence microscopy using a Zeiss LSM 700 Series ConfocalFluorescence Microscope. The excitation wavelengths were 488 nm (2.0%laser power) and 555 nm (2.0% laser power); the emission wavelength wasabout 512 nm; the scan area was 128×128 microns; and the Z step widthwas 0.5 microns. Confocal microscopy showed uniform fluorescencethroughout the grafted lenses which is consistent with the graftingreaction occurring randomly and equally distributed throughout theentire lens under the grafting conditions used in this experiment.

Example 35

A reactive monomer mixture was formed by mixing the reactive componentslisted in Table 13. This formulation was filtered through a 3 μm filterusing a heated or unheated stainless steel or glass syringe and degassedby applying vacuum (about 40 mm Hg) at ambient temperature for about 10minutes. With a nitrogen gas atmosphere and about 0.2 percent oxygengas, 75 μL of the reactive mixture were dosed into the FC. The BC wasthen placed onto the FC. A plate containing about four pallets, eachpallet containing eight lens mold assemblies, was transferred into anadjacent glove box maintained at 50-60° C., and the lenses were curedfrom the top and bottom for 15 minutes using 435 nm LEDs havingintensity of 5.25 mW/cm². The light sources were about six inches abovethe trays. The lenses were stored protected from any additional exposureto light and de-molded and hydrated at later times.

Working under yellow lights and limiting general exposure to light(e.g., by wrapping containers with aluminum foil), the lenses weremanually de-molded with most lenses adhering to the FC and released bysuspending and rolling about 32 lenses in about 500 mL of 70 percent IPAovernight, followed by washing two times with 70 percent IPA, two timeswith 25 percent IPA, three times with deionized water, and finallystored in deionized water in the refrigerator in covered containers forsubsequent grafting experiments. Each washing step lasted about 30minutes. A person of ordinary skill recognizes that the exact lensrelease process can be varied depending on the lens formulation and moldmaterials, regarding the concentrations of the aqueous isopropanolsolutions, the number of washings with each solvent, and the duration ofeach step. The purpose of the lens release process is to release alllenses without defects and transition from diluent swollen networks tothe deionized water or packaging solution swollen hydrogels.

About 10 lenses were suspended in 50 mL of a 1000 ppm solution offluorescein acrylamide[N-(3′,6′-dihydroxy-3-oxo-3H-spiro[isobenzofuran-1,9′-xanthen]-5-yl)acrylamide]in 50:50 (w/v) aqueous TPME in a 100 mL glass jar and degassed for 20minutes under reduced pressure (ca. 40 mm Hg) and purged with nitrogengas aeration. The jar was capped and transferred into glove box with anitrogen gas atmosphere with less than 0.2 percent oxygen gas and atemperature of 60° C. and equilibrated on a shaker for about 90 minutes.The cap was replaced by a clear plastic cover, and the suspension wasirradiated using TL03 light bulbs from the top having an intensity ofabout 4 mW/cm² for about 25 minutes while still being shaken. Afterirradiation, the lenses were removed and washed four times with 70% IPA,three times with deionized water and two times with borate bufferedpacking solution. The grafted lenses were uniformly yellow in color andstored in jars in borate buffered packing solution.

A hydrated grafted lens was staged and subjected to confocalfluorescence microscopy using a Zeiss LSM 700 Series ConfocalFluorescence Microscope. The excitation wavelengths were 488 nm and 555nm; the emission wavelength was about 512 nm; the scan area was 128×128microns; and the Z step width was 0.5 microns. The laser power wasadjusted depending on the concentration of the chromophore in thesample, typically between 0.1% and 15% laser power. Confocal microscopyshowed uniform fluorescence throughout the grafted lenses which isconsistent with the grafting reaction occurring randomly and equallydistributed throughout the entire lenses.

TABLE 13 Weight Percent Component Example 34 mPDMS 31 SiMAA 28 DMA 25HEMA 6 PVP K90 7 TEGDMA 2 Irgacure 819 1 Σ RMM Components 100 MonomerContent in RMM 70 Diluent D3O 100 Diluent Content in RMM 30

Example 36

This example was based azoperester free radical polymerizationinitiators in which the first activation mode was irradiation and thesecond mode was thermal. In particular, tert-butyl7-methyl-7-(tert-butylazo)peroxyoctanoate was synthesized as describedin Macromolecules 2003, 36, 3821-3825, and as shown schematically in thefollowing Scheme:

All NMR spectra (500 MHz) were run in CDCl₃ unless otherwise specified.All chemical shifts are in ppm from TMS. All the reagents and solventswere purchased from Sigma-Aldrich and were used without furtherpurification. tert-Butyl 7-methyl-7-(tert-butylazo)peroxyoctanoate wasused to make a crosslinked substrate network by ultraviolet irradiationwith covalently bound peroxyester groups which was then used to form agrafted polymeric network by a thermally induced free radicalpolymerization.

tert-Butyl 6-bromohexanote (B): To a stirred solution of anhydroustert-butanol (31.29 mL, 0.586 mol) and triethylamine in anhydrous DCM(100 mL) was added 6-bromohexanoyl chloride (25.00 g, 0.117 mol) dropwise at 0° C. and stirred the reaction mixture at room temperatureovernight. Upon completion, water (100 mL) was added and extracted withDCM (2×50 mL). The combined organic extracts were washed with aqueousNaHCO₃ (2×25 mL), brine (25 mL), dried over Na₂SO₄, filtered andconcentrated. The crude product was passed through silica-gel column andeluted with 10% ethyl acetate in hexanes to afford (B) as clear oil in71% yield. ¹H NMR (500 MHz, CDCl3): 3.36-3.42 (t, 2H), 2.18-2.24 (t,2H), 1.80-1.91 (m, 2H), 1.54-1.66 (m, 2H), 1.37-1.50 (m, 11H).

tert-Butyl 6-iodohexanote (C): tert-Butyl 6-bromohexanote (8.00 g, 31.9mmol) was dissolved in acetone (50 mL), NaI (4.78 g, 31.9 mmol) wasadded, and the mixture was refluxed under nitrogen in the dark for 10hours. Solvent was then removed, and the crude product was taken up indiethyl ether (50 mL) and filtered to remove NaBr. Solvent wasevaporated under reduced pressure, and the crude product was passedthrough silica-gel column and eluted with 5% ethyl acetate in hexanes toafford (C) as clear oil in 98% yield. ¹H NMR (500 MHz, CDCl₃): 3.16-3.21(t, 2H), 2.19-2.25 (t, 2H), 1.78-1.89 (m, 2H), 1.54-1.66 (m, 2H),1.36-1.47 (m, 11H).

Acetone tert-butyl hydrazine (E): tert-Butyl hydrazine hydrochloride(25.80 g, 207.1 mmol), potassium hydroxide (26.10 g, 465.2 mmol) andacetone (26.10 g, 449.4 mmol) were mixed together and stirred at roomtemperature under nitrogen for 3 hours. Upon completion, the supernatantliquid was decanted into another flask, the remaining liquid wascarefully removed under reduced pressure, and the residue was purifiedby distillation at 60° C. (76.0 mm Hg) to afford (E) as clear oil in 71%yield. ¹H NMR (500 MHz, CDCl₃): 1.91 (s, 3H), 1.70 (s, 3H), 1.16 (m,9H).

tert-Butyl 7-Methyl-7-(tert-butylazo)octanoate (F): To a solution ofacetone tert-butyl hydrazone (1.0 g, 7.8 mmol) in THE (20 mL) at −78° C.was added MeLi (8.2 mmol, 5.1 mL of 1.5 M in hexane). After the solutionhad been stirred for 1.5 h at −78° C., HMPA (1.4 g, 7.8 mmol) was added;then a solution of tert-butyl 6-iodohexanote (2.4 g, 8.0 mmol) in THE (5mL) was added. The solution was stirred for another 30 min at −78° C.,slowly warmed to room temperature, and stirred for 3 more hours. Ether(40 mL) was added, and the organic solution was washed with water andthen brine. After drying over Na₂SO₄ and filtered, the solvent wasremoved by rotary evaporation. The product (F) (1.2 g, 52%) was obtainedby flash column chromatography on silica gel (ethyl acetate-hexanes,1:20). ¹H NMR: 1.07 (s, 6H), 1.14 (s, 9H), 1.15-1.30 (m, 4H), 1.43 (s,9H), 1.50-1.62 (m, 4H), 2.15-2.21 (t, 2H).

7-Methyl-7-(tert-butylazo)octanoic acid (G): tert-Butyl7-Methyl-7-(tert-butylazo)octanoate (2.00 g, 67.01 mmol) was dissolvedin TFA:DCM (1:1, 25 mL) at 0° C. and stirred at same temperature for 15minutes, followed by room temperature for 1-2 hours. Upon completion,the solvent was removed and the crude product was purified by silica-gelcolumn and eluted with 10% ethyl acetate in hexanes to afford (G) asclear oil in 99% yield. ¹H NMR (500 MHz, CDCl₃): 1.07 (s, 6H), 1.14 (s,9H), 1.18-1.39 (m, 4H), 1.57-1.65 (m, 4H), 2.30-2.36 (t, 2H).

tert-Butyl 7-methyl-7-(tert-butylazo)peroxyoctanoate (H): To a stirredsolution of 7-methyl-7-(tert-butylazo)octanoic acid (1.40 g, 5.69 mmol)in anhydrous THE (5 mL) was added a solution of 1,1′-carbonyldiimidazole(1.20 g, 7.40 mmol) in anhydrous THE (15 mL) slowly, the mixture wasstirred at room temperature for 1 hour and then cooled to 0° C.(ice-bath) and thereafter tert-butyl hydroperoxide (0.821 g, 9.11 mmol)was added and stirred under nitrogen for 6 hours at room temperature.Upon completion, diethyl ether (50 mL) was added to the reaction mixturewhich was stirred for 30 more minutes. The reaction mixture was thenwashed with 10% NaOH (25 mL) and water (50 mL), dried over Na₂SO₄,filtered and concentrated under reduced pressure to afford a crude oilthat was purified by silica-gel column and eluted with 5% ethyl acetatein hexanes to afford (H) as clear oil in 75% yield. ¹H NMR (500 MHz,CDCl₃): 1.05 (s, 6H), 1.12 (s, 9H), 1.15-1.34 (m, 4H), 1.30 (s, 9H),1.54-1.67 (s, 4H), 2.24-2.30 (t, 2H).

55 Milligrams (0.18 mmol) of compound (H) were dissolved in 9.95 grams(32.9 mmol) of TEGDA in a round-bottom flask and degassed under vacuum(ca. 1 mm Hg) for 15 minutes. The vacuum was broken with nitrogen gasand the flask transferred into a glove box set up for photocuring at 60°C. and 0-0.2% oxygen gas. About 100 microliters of this reactive mixturewere added to each FC in a pallet. Each pallet held eight FC. A quartzplate was placed on top of the pallets to hold the FC in place. Thereactive mixtures were irradiated using an UVA lamp (P339 bulbs withpeak output at 312 nm and an intensity of 3.7 mW/cm² at the palletlocation) for 2 hours located three inches above the quartz plate. Thelens-like plugs were placed in 100 mL of DMF in a jar, and the jarplaced on a roller and rolled over the weekend. Lenses were stored inDMF.

10 Lens-like plugs were removed from the DMF suspension and transferredinto a 250 mL 3-necked round bottom flask containing 20 mL of DMA and 80mL of DMF and equipped with a condenser, magnetic stirring bar, aseptum, nitrogen gas inlet, and nitrogen gas outlet on top of thecondenser. The lens-like plugs were stirred for 2 hours during the lasthour with nitrogen gas purging. The lens-like plug suspension was heatedto 130° C. for 5 hours and allowed to cool down to room temperature.

The grafted lens-like plugs were transferred into ajar containing 500 mLof acetone to extract unreacted monomer and solvent. After about 24hours, the acetone was replaced with fresh acetone. The graftedlens-like plugs were stored in acetone.

Un-modified lens-like plugs were taken through the same solventtreatments without thermally induced free radical polymerization. Boththese un-modified and grafted lens-like plugs were vacuum dried at 60°C. overnight in a vacuum oven (<1 mm Hg). 5 Un-modified lens-like plugswere weighed on an analytical balance and their weights summed to 0.1095grams. 5 Grafted lens-like plugs were weighed on an analytical balanceand their weights summed to 0.1138 grams, representing a 3.9 weightpercent increase in mass over the un-modified lens-like plugs. The aboveexperiment was repeated except that grafting reaction at 130° C. lastedfor 17 hours instead of 5 hours. In that case, a 6.6 weight percentincrease in mass was observed for the grafted lenses over theun-modified lens-like plugs.

1. A polymer composition formed by a process comprising: (a) providing afirst reactive composition containing: (i) a polymerization initiatorthat is capable, upon a first activation, of forming two or more freeradical groups, at least one of which is further activatable bysubsequent activation; (ii) one or more ethylenically unsaturatedcompounds; and (iii) a crosslinker; (b) subjecting the first reactivecomposition to a first activation step such that the first reactivecomposition polymerizes therein to form a crosslinked substrate networkcontaining a covalently bound activatable free radical initiator; (c)combining the crosslinked substrate network with a second reactivecomposition containing one or more ethylenically unsaturated compounds;and (d) activating the covalently bound activatable free radicalinitiator of the crosslinked substrate network such that the secondreactive composition polymerizes therein with the crosslinked substratenetwork to form a grafted polymeric network and a byproduct polymer. 2.The polymer composition of claim 1 wherein step (d) is conducted in thepresence of a crosslinker such that the byproduct polymer is covalentlybound with the grafted polymeric network.
 3. The polymer composition ofclaim 1 wherein step (d) is conducted in the substantial absence of acrosslinker such that at least a portion of the byproduct polymer is notcovalently bound to the grafted polymeric network.
 4. The polymercomposition of claim 1 wherein the one or more ethylenically unsaturatedcompounds of step (a) comprise one or more reactive groups independentlyselected from: (meth)acrylate, (meth)acrylamide, styryl, vinyl, N-vinyllactam, N-vinylamide, O-vinylether, O-vinylcarbonate, O-vinylcarbamate,C₂₋₁₂ alkenyl, C₂₋₁₂ alkenylphenyl, C₂₋₁₂ alkenylnaphthyl, and C₂₋₆alkenylphenyl-C₁₋₆ alkyl.
 5. The polymer composition of claim 1 whereinthe one or more ethylenically unsaturated compounds of step (c) compriseone or more reactive groups independently selected from: (meth)acrylate,(meth)acrylamide, styryl, vinyl, N-vinyl lactam, N-vinylamide,O-vinylether, O-vinylcarbonate, O-vinylcarbamate, C₂₋₁₂ alkenyl, C₂₋₁₂alkenylphenyl, C₂₋₁₂ alkenylnaphthyl, and C₂₋₆ alkenylphenyl-C₁₋₆ alkyl.6. The polymer composition of claim 1 wherein the polymerizationinitiator is a bisacylphosphine oxide, a bisacylphosphane oxide, a diazocompound, a di-peroxide compound, an azo-bis(monoacylphosphine oxide),an azo-bis(monoacylphosphane oxide), a peroxy-bis(monoacylphosphineoxide), a peroxy-bis(monoacylphosphane oxide), an azo-bis(alpha-hydroxyketone), a peroxy-bis(alpha-hydroxy ketone), an azo-bis(1,2-diketone), aperoxy-bis(1,2-diketone), a germanium based compound, tert-butyl7-methyl-7-(tert-butylazo)peroxyoctanoate, or combinations thereof. 7.The polymer composition of claim 1 wherein the polymerization initiatoris a bisacylphosphine oxide or a bis(acyl)phosphane oxide.
 8. Thepolymer composition of claim 1 that is in the form of a hydrogel andwherein the first reactive composition contains silicone reactivecomponents and the second reactive composition contains hydrophilicreactive components.
 9. The polymer composition of claim 1 that is inthe form of a hydrogel and wherein the first reactive compositioncontains hydrophilic reactive components and the second reactivecomposition contains silicone reactive components.
 10. The polymercomposition of claim 1 wherein the first reactive composition furthercomprises one or more of a polyamide, a UV-VIS absorber, a dye, a tint,a pigment, an antimicrobial, a pharmaceutical, and a nutraceutical. 11.The polymer composition of claim 1 wherein the second reactivecomposition further comprises one or more of a polyamide, a UV-VISabsorber, a dye, a tint, a pigment, an antimicrobial, a pharmaceutical,and a nutraceutical.
 12. A medical device comprising the polymercomposition of claim
 1. 13. An ophthalmic device comprising the polymercomposition of claim
 1. 14. The ophthalmic device of claim 13 selectedfrom the group consisting of a contact lens, an intraocular lens, apunctal plug and an ocular insert.
 15. A contact lens comprising apolymer composition, wherein the polymer composition is formed by theprocess of claim
 1. 16. The contact lens of claim 15 wherein the firstreactive composition, the second reactive composition, or both the firstreactive composition and the second reactive composition contain one ormore additives selected from UV absorbers, photochromic compounds,pharmaceutical compounds, nutraceutical compounds, antimicrobialcompounds, reactive tints, pigments, copolymerizable dyes,non-polymerizable dyes, release agents, wetting agents, and releaseagents.
 17. A crosslinked substrate network containing a covalentlybound activatable free radical initiator, wherein the crosslinkedsubstrate network is formed by a process comprising: (a) providing afirst reactive composition containing: (i) a polymerization initiatorthat is capable, upon a first activation, of forming two or more freeradical groups, at least one of which is further activatable bysubsequent activation; (ii) one or more ethylenically unsaturatedcompounds; and (iii) a crosslinker; and (b) subjecting the firstreactive composition to a first activation step such that the firstreactive composition polymerizes therein to form the crosslinkedsubstrate network containing a covalently bound activatable free radicalinitiator.
 18. A process for making a polymer composition, the processcomprising: (a) providing a first reactive composition containing: (i) apolymerization initiator that is capable, upon a first activation, offorming two or more free radical groups, at least one of which isfurther activatable by subsequent activation; (ii) one or moreethylenically unsaturated compounds; and (iii) a crosslinker; (b)subjecting the first reactive composition to a first activation stepsuch that the first reactive composition polymerizes therein to form acrosslinked substrate network containing a covalently bound activatablefree radical initiator; (c) combining the crosslinked substrate networkwith a second reactive composition containing one or more ethylenicallyunsaturated compounds; and (d) activating the covalently boundactivatable free radical initiator of the crosslinked substrate networksuch that the second reactive composition polymerizes therein with thecrosslinked substrate network to form a grafted polymeric network and abyproduct polymer.